CLINSQUARE: CLINICAL RESEARCH COURSES
Tuesday, December 24, 2024
CLINSQUARE: Clinical Rsearch Courses by LIFEPRONOW
Home Blog Page 145

FDA approved AstraZeneca’s Farxiga(dapagliflozin) for Priority Review for the patients with heart failure with reduced ejection fraction

admin
-
0
FDA approved AstraZeneca’s Farxiga(dapagliflozin) for Priority Review for the patients with heart failure with reduced ejection fraction

Jan 06, 2019: AstraZeneca announced the U.S. FDA has accepted a supplemental New Drug Application (sNDA) and granted Priority Review for Farxiga (dapagliflozin) in order to reduce the risk of cardiovascular (CV) death or the worsening of heart failure (HF) in adults with heart failure and reduced ejection fraction (HFrEF) with and without type-2 diabetes (T2D). 

Farxiga is the first-in-class, oral once-daily selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2).

The sNDA was based on the results from the landmark Phase III DAPA-HF trial published in Sep 2019 in The New England Journal of Medicine, which showed Farxiga on top of standard of care reduced the incidence of the complex result of CV death or the worsening of HF versus placebo.

Farxiga is indicated as a monotherapy and as part of combination therapies in order to improve glycaemic control in adults with T2D. In October 2019, the FDA also approved Farxiga to reduce the risk of hospitalisation for the heart failure in patients with T2D and established cardiovascular disease or multiple CV risk factors. https://www.astrazeneca.com/media-centre/press-releases/2020/farxiga-granted-fda-priority-review-for-patients-with-heart-failure-with-reduced-ejection-fraction-06012020.html

Want to become a Pharmacist in U.S.? Then follow the journey to registration

admin
-
0
Want to become a Pharmacist in U.S.? Then follow the journey to registration

Becoming a U.S. citizen is difficult, but it is doubly difficult to become a Pharmacist in the U.S. It’s a highly competitive industry, possibly because the U.S. is one of the dynamic forces that is pushing the global pharmacy profession forward.

And, pharmacists in the U.S. are among the highest-paid pharmacists in the world, earning an average salary of around $120,950, according to the U.S. Department of Labor Bureau of Labor Statistics. Also, there are tons of benefits of becoming a pharmacist in the U.S., including:many opportunities for continuing education, the ability to practice in a variety of clinical settings, a strong community of the Pharmacy professionals and a salary that can provide a good standard of living.

If you are making an allowance for becoming a pharmacist in the U.S., here’s some information that will definitely help you achieve your goal. The journey to registration is as follows:

1. Apply to Education Credential Evaluators (ECE) in order to gain recognition of equivalence of your foreign qualifications. The spirit of the application is to demonstrate that your foreign undergraduate training is equal to that of someone educated in the US.The ECE requires two copies of the following documents: official university transcript proof of degree https://www.ece.org/

2. Apply to the National Board of Pharmacy (NABP) to start the Foreign Pharmacy Graduates Equivalency Committee certification process The NABP requires a single copy of your pharmacy registration document. Records sent to the ECE and NABP from the issuing education institution (either directly or via you) must be in a sealed envelope with the issuing body’s stamp over the seal. An application with demographic information also needs to be certified by a US-based notary. Once the NABP receives a satisfactory general evaluation report from the ECE,  it will then send you an authorisation to test letter (ATT) allowing you to sit in the Foreign Pharmacy Graduate Equivalency Examination (FPGEE). https://nabp.pharmacy/

3. Register online for the FPGEE and the test of English as a foreign language internet-based test (TOEFL ibt) The FPGEE is held bi-annually at a Pearson VUE Test Centre. The TOEFL ibt is available frequently at an Educational Testing Service Centre. These examinations can be done in any order, If English is not your first language, you might want to study for the FPGEE first.

4. Register as a pharmacy intern with the state board of pharmacy and start recording working  hours This can be done as soon as you are approved to sit in the FPGEE. You will need to find a pharmacist who will be your instructor at your internship facility and register as a pharmacy intern with the State Board of Pharmacy. Once got registered, start “recording” 500 to 1,500 intern hours (depending on the state). https://www.pharmacyexam.com/?gclid=Cj0KCQiA04XxBRD5ARIsAGFygj_XgIbvP4Vluhz6emU0weXlDCz6nQPTBUrS6O7RIYEAEAfdyMCIexsaAqazEALw_wcB

5. Take the FPGEE and the TOEFL ibt Results for the FPGEE can take around eight weeks to arrive. Results for the TOEFL ibt are available online within 10 days. Once you have set both of these tests, your entire assortment undergoes final evaluation by the FPGEC (which can take up to 10 weeks) before you are issued with a certificate. https://www.ets.org/toefl

6. Submit records of internship hours to the State Board of Parmacy/PCS once completed This has to be done before you apply for the North American Pharmacy Licensure Examination (NAPLEX) and Multistate Jurisprudence Pharmacy Examination (MJPE). Use the proper form and be prepared to submit proof of worked hours.

7. Once approved, apply for and take the NAPLEX and the MJPE and apply for pharmacy licensure Eligibility to take these examinations also varies according to state and your local board needs to issue another ATT first. In Massachusetts there is a combined form for the NAPLEX, MJPE and pharmacy licensure (again there is a demographic component and it needs notarising). An MJPE must be passed in every state a candidate wishes to practise in, since pharmacy law varies from state to state. Other things to consider can be some additional costs, such as: Charges for issuing documentation, notary fees, textbooks/online resources, postage and packaging and any examination repeat fees. Pharmacist’s salaries are higher in the US that can  provide Financial support while applying for the job. In hospital pharmacy, working patterns incorporate variable shift-work. https://nabp.pharmacy/programs/naplex/

  FPGEE TOEFL ibt NAPLEX MJPE
When it can be taken Bi-annually at dates set by NABP (usually April,September)  Any time  Any time  Any time 
Style of examination 250 multiple choice questions on anything from  undergraduate degree. Some familiarity is needed with US-specific pharmacy (eg,law, drug names, terminology, the healthcare model)  Reading, writing, listening and speaking sections.Computerised test with a series of questions.  185 MCQs to test ability to measure pharmacotherapy and therapeutic outcomes, prepare and dispense medicines, and implement and evaluate information. Often in a scenario-based format. Similar in content to theUK registration assessment  90 MCQs. Combines federal- and state-specificquestions to test pharmacy jurisprudence knowledge 
Test centre Any Pearson VUE Test site Any ETS Test site Any Pearson VUE Test site Any Pearson VUE Test site  
Length of examination 5.5 hours (30 minutes’ break in middle)  Four hours (10 minute break in the middle)  4.25 hours (optional 10 minute break)  Two hours (nobreak) 
Cost ($1?£0.65) $800 for examination and $85 for ECE report. Approximately $400 for copies of reports to be sent to ECE and NABP, notary fees, postage and packaging, registration as intern and registration as pharmacist $160 $421 (combined total for NAPLEX, MJPE, licensure application). May vary depending on state. $421 (combined total for NAPLEX, MJPE, licensure application). May vary depending on state.
Pass mark  Scaled score of 75 (range 0–150) Speaking 26 Writing 24 Listening 18 Reading 21    Scaled score of 75  Scaled score of 75 

How to Become a Pharmacist in the U.S. – For Non-U.S. Citizens

https://www.pharmaceutical-journal.com/test-tomorrows-pharmacist/tomorrows-pharmacist/how-to-gain-your-licence-to-practise-as-a-pharmacist-in-the-us/11128041.article?firstPass=false

Drug Approval Process in India

admin
-
0
Drug Approval Process in India

Regulatory Bodies for Drug approval in India

The Drug and Cosmetic Act 1940 and Rules 1945 was enacted to regulate the import, manufacture, distribution and sale of drugs and cosmetics in India. The Central Drugs Standard Control Organization (CDSCO) is the regulatory body (as FDA in the USA) in India and drug controller general of India heads the CDSCO.

In 1988, the Indian parliament added Schedule Y to the Drug and Cosmetics Rules 1945. It provides the guidelines and requirements for clinical trials. It was further amended in 2005 to make it more aligned with international standard.

Definition of New drug :

Rule 122E under The Drug and Cosmetic Act 1940 and Rules 1945 defines the ‘new drug:

“drug, including bulk drugs substance (or phytopharmaceutical drug) which has not been used in the country to any significant extent under the conditions prescribed, recommended or suggested in its labelling and has not been recognised as effective and safe by the licensing authority for the proposed claims, drugs already approved for certain claims, which are now proposed to be marketed with modified or new claims (viz., new indications, dosage, dosage forms or routes of administration), or fixed-dose combinations of two or more drugs, individually approved earlier for certain claims, which are now proposed to be combined for the first time in a fixed ratio, or a new fixed ratio, with certain claims, (viz., indications, dosage, dosage forms or routes of administration)”

It is important to point out that “new drug shall continue to be considered as a new drug for a period of four years from the date of its first approval or its inclusion in the Indian Pharmacopoeia whichever is earlier”

Information and data required for approval of clinical trial and/or to import or manufacture of a new drug for marketing in India are clearly described in 122A, 122B and 122D, 122DA, 122DAA, 122E rules of Drugs and Cosmetics Rules and Appendix I, IA and VI of Schedule Y.

Form 29: Applicant/Sponsor has to take NOC from CDSCO. Based on this, the applicant can take license in form 29 from the state Licensing authority to manufacture test batches of new drugs (for development and generation of data).

New Drug Approval Process in India:

  • New drug candidate being developed in India and not Marketed anywhere else.
  • New Drug candidate being developed outside India and not marketed anywhere in the world.
  • If the drug is already approved/marketed in other countries but not approved in India.
  • Drug candidate which are approved in other countries and being used from several years:

New drug Discovered in India and not Marketed anywhere else:

If a new substance is discovered in India and not approved in any part of the world, then all Phases of the trial (Phase I to Phase III)  needs to be conducted to get the Market authorization.

New Drug candidate being developed outside India and not marketed anywhere in the world.

An applicant has to submit Phase I data along with the application. Licensing Authority reviews the Phase I data and Based on this, they may grant permission to conduct Phase II and subsequent Phase III trial in India concurrently with another global trial of a drug candidate. It is also possible that regulatory authority may ask to repeat the Phase I trial in India.

If the drug is already approved/marketed in other countries but not approved in India.

  • In general, if a drug candidate is approved in one or more countries like USA, UK, Canada, European Union, Japan, and Australia, then it will be considered for approval of manufacture/import and marketing in India.
  • If the sponsor is seeking approval of the drug candidate in India which is already have been approved/Marketed in other countries,  then sponsor or applicant has to conduct Phase 3 data on at least 100 subjects across 3 to 4 centre to confirm the safety and efficacy of drug candidate in  Indian population.
  • The regulatory authority may ask any additional non-clinical and clinical data based on the nature of drug candidate and information available
    It is important to note that if a drug candidate is discovered in India and it is not marketed in any other countries,  then the applicant has to conduct Phase 3 studies in 500 subjects across 10 to 15 centre.

Scenarios when clinical trials are not required to be conducted for drug approval in India

If the drug is approved in other countries and applicant is seeking approval to market/manufacture/import this drug in India then it is not necessary to conduct clinical trials in India if drug candidate meets any of the following requirements.

The requirement of submitting results of local clinical trials may not be necessary As per the provisions given in the Drugs & Cosmetics Rules.

  • serious/life-threatening condition,
  • Diseases which carries special relevance in Indian Population
  • No satisfactory  therapeutic option available 
  • Unmet medical need exist
  • Rare Disease
  • If a drug candidate offers added a significant advantage over the existing treatment options for a specific disease

Drug candidate which are approved in other countries and being used from several years:

In this case, a clinical trial may be waived off in India as per rule 122 A of drug and cosmetic Act if the sufficient published safety data is available, however, how many years will be considered as “ several years” is not clear.

Important facts:

Category A: Clinical trial   (approved in the U.S., Britain, Switzerland, Australia, Canada, Germany, South Africa, Japan and the European Union) are eligible for fast-tracking.  Because these clinical trials have been approved already by a competent and robust process by a well developed regulatory framework, so the India regulatory authorities can rely on data to some extent for dug approval in India.

Category B: Apart from above, All trial falls under B. India Regulatory authority reviews the data and scrutiny process takes 16-18 weeks.

Investigational New Drug Application (IND): Data of chemistry, manufacturing, control and animal studies needs to be submitted to regulatory authority along with other documents such as protocol, investigator’s brochures (IB), and informed consent documents. A copy of this application needs to be submitted to the ethical committee as well. DCGI reviews this application and applicant can conduct a clinical trial in India once it gets approval for this.

New Drug Application: New Drug Registration using form 44 along-with preclinical, clinical and other relevant data such as marketing status in other countries, testing protocol, label, product monograph, needs to be submitted to the regulatory agency. It may take 12-18 months to review the application.

Approval of Drugs in India, with some modification over existing approved drug

Pharmaceutical companies may change an already approved  product in many ways namely:

  • New proposed Indications
  • Change in dosage 
  • dosage form (including sustained release dosage form)/formulation change
  • Route of administration (ie oral from IV)

This type of application differs from the New drug applications as in this case, drug regulatory agency relies on safety and efficacy data of already approved drug at least in part.

Please note this pathway or application is like an sNDA in The regulatory authority may ask some additional clinical or non-clinical data which is decided by case by case basis.

In the below scenario, the regulatory authority may require less or no additional data of  Animal Pharmacological, Animal Toxicological and clinical studies.

  •  If the drug is already approved by other countries for the proposed indication
  • Availability of evidence showing no difference in the metabolism of the drug due to ethnic differences
  •  Clinical data is available supporting benefit-risk ratio in favour of drug  candidate for the proposed new claim 
  • Package insert from other countries shows that there is no new safety concern if the drug is given to the Indian patient for the new claim.
  •  if new claim covers serious or life-threatening diseases or any disease which are quite relevant to India

Note: Comparative clinical trials and bio-equivalence study comparing the modified release formulation with the immediate-release formulation is required to be conducted if the applicant seeks approval for Modified release product. In case if the proposed formulation is already approved then comparative bio-equivalence study is recommended. Further guidance can be sought from CDSCO.

You can follow the blog of Fixed-Dose Combination Approval Process to have a better understanding of how India is approving fixed-dose combination.

Ref: https://journals.sagepub.com/doi/full/10.1177/0971721818762931
http://www.globalresearchonline.net/journalcontents/v13-2/004.pdf
https://cdsco.gov.in/opencms/opencms/en/Home/

ECOG Performance Status

admin
-
1
ECOG Performance Status

ECOG Performance Status-scale was developed by Eastern Cooperative Oncology Group. Now this group is a part of ECOG-ACRIN Cancer Research Group.
This scale was published in 1982.

Importance of ECOG performance status:

  • It provides standard criteria to measure the impact of disease on patient’s daily living abilities/performances for example, ability to walk, Office work etc.
  • It helps sponsor to recruit Desired population in oncology studies.
  • It also provides considerable information about treatment effect on patient’s level of functioning.
  • Data Manager can get the information about this while reviewing the protocol in oncology trials as all protocol clearly mentions which performance Grading system needs to be used. (other performance Grading System: Karnofsky Performance Status)
  • Please refer the below table which is taken from ECOG-ACRIN Cancer Research Group website
GradeECOG Performance Status
0Fully active, able to carry on all pre-disease performance without any restriction
1Restricted in the physically strenuous activity but ambulatory and able to carry out work of the light or sedentary nature, e.g., light house work, office work
2Ambulatory and capable of all selfcare but not able to carry out any work activities; up and about more than 50% of waking hours
3Capable of only limited selfcare; confined to bed or chair more than 50% of the waking hours
4Completely disabled; cannot carry on any selfcare; totally confined to the bed or chair
5Dead

Source: https://ecog-acrin.org/resources/ecog-performance-status

Orphan Drug Designation in US, EU and Japan

admin
-
0
Orphan Drug Designation in US, EU and Japan

Orphan Drug Designation in USA:

There are two routes (criteria) for obtaining orphan designation of a drug and biologics for a rare disease or condition.
Orphan drug designation and approval may be granted if application meets one of the following criteria.

(1)If a  product is intended for  treatment, prevention or diagnosis a  disease or condition that has a prevalence of less than 200,000 Individuals in USA.(FDC Act § 526(a)(2)(A))

Or

(2) even if a disease or condition affects 200,000 or more individuals, then also sponsor can seek orphan drug designation for its product.

It can only be possible if a sponsor can show that there is no reasonable expectation that the costs of drug development and making available to market can be recovered by its sale in USA. (FDC Act § 526(a)(2)(B) cost recovery provisions of the act)

Orphan Drug Designation in European Union

In order to get qualified for orphan designation, a drug candidate must meet a number of criteria:

  • Drug candidate must be intended for the treatment, prevention or diagnosis of a life-threatening or chronically debilitating diseases.
  • the prevalence of the condition in the European Union must not be more than 5 in 10,000 or there must be no reasonable expectation that the costs of drug development and making available to market can be recovered by its sale in the EU. 
  • “no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorized, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition” as per EMA

Related: The Drug approval process in EU:
Drug Approval process-FDA

Orphan Drug Designation by JAPAN:

The drug candidate (and Medical Device) Should meet the following criteria to get orphan drug Designation:
The number of patients who may use the drug or medical device should not exceed 50 000 in Japan.

Intended indication for  the treatment of serious diseases, including difficult-to-treat diseases.

“Additionally, they must be drugs or medical devices for which there are strong medical needs that meet one of the following requirements.

1. No appropriate alternative drug/medical device or treatment available
Or

2. High efficacy or safety is expected compared with existing products”
There should be a theoretical rationale for the use of the product for the target disease, and the development plan should be appropriate.” as per MHLW

References: http://www.fdalawblog.net/2009/02/the-rarely-used-cost-recovery-path-to-orphan-drug-designation-and-approval/
https://www.mhlw.go.jp/english/policy/health-medical/pharmaceuticals/orphan_drug.html
https://www.fda.gov/industry/developing-products-rare-diseases-conditions

AVITA medical receives U.S. FDA investigational device exemption approval of clinical feasibility study in order to evaluate Recell system for Vitiligo

admin
-
0
AVITA medical receives U.S. FDA investigational device exemption approval of clinical feasibility study in order to evaluate Recell system for Vitiligo

Dec 30, 2019: AVITA Medical Limited announced that the U.S. FDA has approved the company’s Investigational Device Exemption (IDE) application to conduct a feasibility study evaluating the safety and effectiveness of the RECELL® Autologous Cell Harvesting Device (RECELL® System) for repigmentation of depigmented lesions associated with stable vitiligo.

Vitiligo affects approximately 6.5 million people in the United States, rivalling the predominance of psoriasis. Conversely, there are limited treatment options available to patients to permanently restore skin pigmentation.

Vitiligo is a disease that causes loss of color, or pigmentation, in patches of skin that impacts the quality of life for those living with the condition.

Currently, there is no cure for vitiligo, nor a universally accepted method for limiting the spread of the disease.AVITA Medical will collaborate with a leading medical centre in order to conduct a pilot study with 10 patients, have vitiligo lesions that have been stable for at least one year.

Areas of the vitiligo lesion will be randomly treated with slightly altering cell suspensions prepared using RECELL to confirm response rates and best possible suspension parameters. https://www.avitamedical.com/uploads/pdf/AVH-Press-Release-Vitiligo-IDE-Approval-30DEC2019-FINAL.pdf

The Drug approval process in EU:

admin
-
0
The Drug approval process in EU:

50 regulatory authorities from the 31 European Economic Area (EEA) countries (28 EU Member States, including Iceland, Liechtenstein and Norway), the European Commission and EMA creates the European medicines regulatory system.

European medicines regulatory system= (European commission + EMA + 50 Regulatory authorities)

This network makes EU regulatory system unique and quite complex. Although this is not its official name, the EMA is also called the European Medicines Assessment Agency or EMEA. It is currently called The European Agency for Medicines.

Before Proceeding into approval process, let’s learn about two common terminologies.

Clinical Trial Application (CTA). It consists of comprehensive information about the investigational medicinal product and details about the proposed/planned trial. Regulatory authority reviews this application and decides about acceptability of conducting a trial.

It can be considered as equivalent to IND (Investigational new drug application) which needs to be submitted to FDA to get permission to initial a trial.

Marketing Authorization Application (MAA): It is an application submitted by a drug manufacturer/sponsor seeking permission to bring a drug product to the market. It can be consider as Equivalent to NDA of US regulatory

The below information covers only drug for human use.

There are four approval paths:

  • Centralised procedure
  • Decentralised procedure
  • Mutual-recognition procedure
  • Nationalized Procedure

Centralized procedure:

  • It allows the marketing of a drug candidate on the basis of a single EU-wide assessment and marketing authorisation which is valid throughout the EU (European Union).
  • Pharmaceutical companies or Sponsor has to submit single application to EMA and The Agency’s Committee for Medicinal Products for Human Use (CHMP) carries out a scientific assessment of the application and gives a recommendation to the European Commission. Based on the recommendation, marketing authorisation can be granted or rejected.
  • Once it is approved, it is valid for all EU member state. The whole process may take around 210 days

Important Note:

The centralized procedure is compulsory in below scenario:
If Human Medicine contains new active substance to treat

  • Cancer, Diabetes, Auto-immune disease, Orphan medicines, products manufactured by mean of biotechnology processes, neurodegenerative disorder, other immune dysfunctions, HIV and viral diseases.
  • Gene-therapy, somatic cell-therapy or tissue-engineered medicines;

It is optional for other medicines:

  • New active substances for  indication other than listed above
  • Significant therapeutic, scientific or technical innovation;
  • Whose authorisation would be in the interest of public health at EU-Level.

Decentralised procedure: 

  • In this procedure the applicants/sponsor can apply for marketing authorization in more than one European Union Member States for those products which have not been yet authorized in any European Union country and also do not come under the list of drugs under compulsory Centralized Procedure category (List mentioned above under “important note”)
  • The whole process may take around 210 days

Mutual Recognition Procedure:
Where applicant/Sponsor that have a drug authorized in one EU member states, can apply for this authorization to be recognized in other EU countries. Member States has to rely on each other’s scientific assessments

  • The member state, where drug is already approved, is called reference member state and concerned member states are the one where applicant is seeking the approval through this process.
  • This whole process can take up to a time period of 390 days.

Nationalized Procedure: In this procedure the applicant is allowed to obtain a marketing authorization in any of the one member states. To get the National Marketing authorization, the applicant needs to submit the application to the competent authority of the member state. It may take up to 210 days.

Generic and Hybrid Medicine approval process:

Generic Medicine:  As per EMA:

“A generic medicine contains the same active substance(s) as the reference medicine, and is used for treating the same disease(s) at the same dose(s). Nevertheless, the inactive ingredients of a generic drug can be specific in name, appearance and packaging.”

Since the safety and efficacy data of the active substance is already available from the reference drug, sponsor/applicant only need to product below information:

  • information on the quality of the medicine;
  • bioequivalence study

Conceptually It is like FDA’ 505 (j) pathway for Generic Drug approval with no Changes or few allowed changes.

Hybrid medicines: As per EMA:

  • Authorization  of Hybrid medicines  depends partly on the results of tests on the reference medicine and partly on new data from clinical trials (New + Old Data)

Hybrid Medicines carries the same active ingredient (as Reference Medicine) but it but has a different strength/route of administration or a slightly different indication from the reference medicine.

  • Additional Clinical trial may be required to test efficacy and/or safety.
  • Conceptually It is like FDA’ 505 b(2) pathway for generic drug with Some changes.

List of Scientific Committees which do the scientific assessment.

Source: https://www.ema.europa.eu/en/documents/leaflet/european-regulatory-system-medicines-european-medicines-agency-consistent-approach-medicines_en.pdf
  • The member state, where the clinical trial is taken place, will be responsible for authorisation and oversight of a clinical trial.
  • The European Clinical Trials Database (EudraCT) tracks all the authorized clinical trial in EU.

Ref: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/generic-hybrid-medicines
https://www.ema.europa.eu/en/documents/leaflet/european-regulatory-system-medicines-european-medicines-agency-consistent-approach-medicines_en.pdf

Big Change in FDA process for Biologics:

admin
-
0
Big Change in FDA process for Biologics:

 “The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) requires that a marketing application for a “biological product” (that previously could have been submitted under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act)) must be submitted as a biologics license application (BLA) under section 351 of the Public Health Service Act (PHS Act).”

This requirement is subject to certain exceptions during a 10-year transition period ending on March 23, 2020.” as per FDA
It means, after 23-Mar-2020, we will have only BLA pathway for biological product. This 10 year period (2009 to 2020) is given to sponsor so that they can be prepared for this transition.

Background of this change:

As we know that some protein (Not chemically synthesized) products; for example  insulin and insulin analogs, human growth hormone (HGH), reproductive hormones, pancreatic enzymes, used to be  approved by new drug applications (NDAs) pathway under the FD&C Act. As per new changes, these products will be shifted to BLA pathway.

Proteins (NDA pathway) before 23-Mar-2020 
Proteins (BLA pathway) After 23-Mar-2020
You can read about biological product approval pathways in below article https://lifepronow.com/blog/2019/12/27/biologics-approval-pathways-in-usa/

Lets Learn about the details of this new process:

For Proposed Product:
After 23-Mar-2020, Biological products which could have been approved by NDA pathway, will be approved by BLA applications. Sponsor needs to submit an application under section 351 of the PHS Act. Based on the nature of product, application can be either:

  1. 351(a) BLA ( “stand-alone” BLA) for new product
  2. 351(k) BLA for a proposed biosimilar product or a proposed interchangeable product.

For approved products:,
“The BPCI Act requires that an approved marketing application for a “biological product” under section 505 of the FD&C Act be deemed to be a license for the biological product (i.e., an approved BLA) under section 351 of the PHS Act on March 23, 2020, and regulated under the PHS Act.”  as per FDA.

  • It means already approved biologics under NDA pathway will be considered as approved (deemed to be a license)  under BLA pathway after 23-Mar-2020.
  • After the transition, sponsor can seek approval of bio-similar or interchangeable biologics of  these transitioned products.

More guidance about interpretation of this act can be found in below link under resource section: https://www.fda.gov/drugs/guidance-compliance-regulatory-information/deemed-be-license-provision-bpci-act


U.S. Food and Drug Administration (FDA) approved sNDA to Revise Flexion Therapeutic’s ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) for the treatment of osteoarthritis (OA) knee pain

admin
-
0
U.S. Food and Drug Administration (FDA) approved sNDA to Revise Flexion Therapeutic’s ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) for the treatment of osteoarthritis (OA) knee pain

Dec. 26, 2019: Flexion Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) to revise the product label for ZILRETTA (triamcinolone acetonide extended-release injectable suspension) for the treatment of osteoarthritis (OA) knee pain.

Some important elements of the label update include Removal of language which stated that ZILRETTA was “not intended for the repeat administration.” The restructured label states that the “efficacy and the safety of repeat administration of ZILRETTA have not been demonstrated.”

Removal of the misleading statement describing a single secondary tentative endpoint in the original Phase 3 pivotal trial which compared ZILRETTA to immediate release triamcinolone acetonide crystalline suspension. 

ZILRETTA is indicated as an intra-articular injection and is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product.

ZILRETTA has not be evaluated and should not be administered by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. It should not be considered safe for epidural or intrathecal administration. https://fda.einnews.com/pr_news/505807715/flexion-therapeutics-announces-fda-approval-of-snda-to-revise-zilretta-triamcinolone-acetonide-extended-release-injectable-suspension-product-label

Biologics Approval Pathways in the USA:

admin
-
0
Biologics Approval Pathways in the USA:

Existing Regulatory framework for biologics approval in the US:

Two laws were enacted to regulate drugs in the USA: The Federal Food, Drug, and Cosmetic Act (21 USC § 301, FD&C), and the Public Health Services (PHS) Act (42 USC § 262; PHS).
FDA was empowered by the US government to enforce the Federal Food, Drug, and Cosmetic Act and other laws including a few section of the Public Health Service Act.

There are two divisions in the FDA: Center for Drug Evaluation and Research (CDER) and The Center for Drug Evaluation and Research (CBER).

CBER deals with biological products exclusively  and CDER mainly regulates Chemical drugs but in 2003 FDA has transferred few biological to CDER. Information about biological which was transferred to CDER is mentioned in the second section of this article.

In 2010, the PHS Act was amended to create an abbreviated approval pathway for biosimilars, or biologics which can be considered “highly similar” or interchangeable with FDA authorized drug (reference drug).

This pathway is also known as the Biologics Price Competition and Innovation Act (BPCIA) of 2010 and it is quite similar in concept with the Hatch-Waxman Act of 1984 for generic drugs.

On June 30, 2003, FDA transferred some of the therapeutic biological products that used to be evaluated and regulated by CBER (Center for Biologics Evaluation and Research) to CDER  (Center for Drug Evaluation and Research).

CDER will take care of regulatory aspects including premarket review and persevering with oversight, over the transferred product. In regulating the products assigned to them, CBER and CDER will seek advice from each other often and on every occasion necessary.

Categories of Therapeutic Biological Products Transferred to CDER

  • Monoclonal antibody (invivo use only)
  • Therapeutic protein (obtained from  plants, animals, or microorganisms, and recombinant protein)
  • Immunomodulators (Except vaccine and allergenic product)
  • Growth factors, cytokines and monoclonal antibodies which are meant to modify the production of hematopoietic cells in in vivo.

    Drug approval Process by CDER

Categories of Therapeutic Biological Products Remaining in CBER

  • Cellular products: Human cells, bacterial or animal cells and components of these cells.
  • Gene therapy products.
  • Vaccines 
  • Allergenic extracts
  • Antitoxins, antivenins, and venoms
  • Blood and Blood components
  • Plasma and Plasma Derived products

For combination products, “Intended mode of action by which part” is checked. If a product is a combination of Drug A and Biological B but Mode of action is due to Biological B then as per the assigned category (see above categories), the application will be transferred to either CDER or CBER.

Present Regulatory Pathway for Biologics in US:
1. 351 (a)
2. 351 (k)
3. 505 b(2)

351(a) or Stand Alone Pathway or BLA (Biological License pathway):
It comes under PHC act and it is a traditional pathway used for approval of innovator biologics. Safety and Effectiveness data need to be submitted along with application. 

It is like New drug application (505 b(1)) pathway for drugs which are reviewed by CDER. Robust information about manufacturing facility is also required in BLA application.

351(k) Pathway: It also comes under PHC act. The application is submitted by the manufacturers in order to get a product reviewed as a biosimilar or interchangeable which is considered to be “highly similar” to an FDA licensed reference product.

Let’s know about FDA given definitions:

Biosimilar or Biosimilarity definition  :

“that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; and 

there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency of the product.” As per FDA

Interchangeable or Interchangeability Definition: 

“the biological product is bio-similar to the reference product; 

it can be expected to produce the same clinical result . as the reference product in any given patient.

for a product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alternation or switch.” as per FDA

Please note that Interchangeable product may be substituted with Ref product without the consent of a Doctor.

Reference Product Definition:

“ the single biological product, licensed under section 351(a) of the PHS Act, against which a biological product is evaluated in an application submitted under section 351(k) of the PHS Act” As per FDA.

 FDA decides which of the following studies are necessary to be included in the application:  
Analytical Studies – Check of comparability between the biological and reference product. It is also done to know any minor difference in clinical inactive ingredients.

Animal Studies – It is done for evaluation of toxicity.

Clinical Studies – Assessment of immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD) to establish the safety of the product in the condition of use.

It is important to note that biological product may not be evaluated against more than one Reference product.

General Requirements of 351(k) pathway

  • Intended product Is biosimilar to a reference product;
  • Mechanism of action should be same as reference product
  • Intended Indication for approval should be same to that of Reference product
  • Same Route of administration
  • Same dosage form, strength as per the reference product
  • Detailed information about facility, where Intended product  is manufactured, processed, packed, or held to ensure its safety, purity and potency.
505(b)(2) Pathway:

Prior to the enforcement of  BPCIA to till today 505(b)(2) pathway could be used for certain biologicals. Similar to 351(k) pathway, this pathway allows the applicant to rely on the safety and effectiveness data of a previously-approved product.

The 505(b)(2) pathway is available for a relatively narrow category of biologics specifically, those that had been approved under an New drug application (NDA) before the BPCIA was signed into law in 2010. Examples can be found at below source. https://www.biologicsblog.com/biosimilars-under-505-b-2-pathway-2

Must Read: Big Change in FDA process for Biologics:

Ref:
https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/transfer-therapeutic-products-center-drug-evaluation-and-research-cder https://www.freyrsolutions.com/what-is-351a-351k



Generic Products Approval Pathways (USA): Paragraph Certification I, II, III, and IV:

admin
-
0
Generic Products Approval Pathways (USA): Paragraph Certification I, II, III, and IV:

Few facts before discussing about generic products approval in US:

  • Hatch-Waxman Act: The Drug Price Competition and Patent Term Restoration Act is commonly known as “Hatch-Waxman Act” which was enacted in 1984 as an amendment to Federal Food, Drug, and Cosmetic Act (the “FFDCA”) and the Patent Act.
  • The main goal of this act to expedite the Generic drug approval process and reach the market quickly.  505 (b)2 and 505(b) (j) regulatory pathways were introduced  by this act.
  • Patent information of all the approved product is maintained in orange book.
  • Abbreviated New Drug application (ANDA) is used for generic products approval in US. It comes under 505 (b)(j) section. It is commonly called as 505 (b)(j) pathway of generic drug approval.
    Learn about other of drug approval in USA
    Drug Approval Process in India
    The Drug approval process in EU
    Drug Approval Process in China

Para I, II, III and IV certifications:

ANDA has four type of submission (Section 505(j)(2)(A)(vii); 21 CFR 314.95). They are listed as :

  • Paragraph I certification: when patent is not submitted for drug candidate (No Patent in Orange book). FDA can approve ANDA without delay.
  • Paragraph II certification: when the  Patent gets expired, FDA can approve ANDA without delay.
  • Paragraph III certification: After the particulate date when drug patent is going to be expired, FDA can approve ANDA.
  • Paragraph IV certification:  It is somewhat complicated. applicant files the application to FDA for ANDA paragraph- IV certification. Applicant has to notify the patent holder about this application within 20 days.

Patent holder can files infringement suit against ANDA applicant within 45 days (from receiving of notification by ANDA applicant). In this case, ANDA approval is stayed for 30 months.

source FDA: https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/UCM445610.pdf)

It is important to note that 180-day exclusivity is only available to “First to File” (FTF) ANDAs which comes successfully through Paragraph IV certification.

Shared Exclusivity:  Many times there are more than one applicant in “First to file” category. In this case, applicant  share the 180 days exclusivity which can be understood by below graph (source FDA:

source FDA: https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/UCM445610.pdf)

Ref: https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2016/8/patents-vs-market-exclusivity-why-does-it-take-so-long-to-bring-generics-to-markethttps://www.fda.gov/media/92548/download

fda.gov/drugs/development-approval-process-drugs/frequently-asked-questions-patents-and-exclusivity#What_is_the_difference_between_patents_a

https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/paragraph-iv-drug-product-applications-generic-drug-patent-challenge-notifications

for IT certification, follow the path: comptia A+ certification test

U.S. Food and Drug Administration (FDA) approved Allergan’s UBRELVY(ubrogepant) for the acute treatment of migraine with or without aura in adults.

admin
-
0
U.S. Food and Drug Administration (FDA) approved Allergan’s UBRELVY(ubrogepant) for the acute treatment of migraine with or without aura in adults.

Dec. 23, 2019: U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for Allergan’s UBRELVY™ (ubrogepant) for the acute treatment of migraine with or without aura in adults.

UBRELVY™ is the first and only orally-administered, highly potent calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start.

Migraine is a neurological disease that is characterized by intermittent migraine attacks with symptoms that are often incapacitating.

Migraine afflicts 31 million Americans and is the thirds general disease and second leading cause of disability worldwide. It provided lasting relief up to 24 hours as well.

UBRELVY™(50 mg,100 mg), block CGRP, a protein that is released during a migraine attack, from binding to its receptors, without constricting blood vessels, which some older treatments are known to do. https://www.allergan.com/News/Details/2019/12/Allergan%20Receives%20US%20FDA%20Approval%20for%20UBRELVY%20for%20the%20Acute%20Treatment%20of%20Migraine%20with%20or%20without%20Au

1...144145146...156Page 145 of 156

EDITOR PICKS

POPULAR POSTS

POPULAR CATEGORY

ABOUT US

LifeProNow provides guidance and high quality contents to help job seekers to get their dream Job. All the contents are written by experienced folks and peer reviewed by experts.

Contact us: [email protected]

FOLLOW US

© LifeProNow | All Rights Reserved