Category: Regulatory Agencies

Increasing Transparency in Drug/Medical Device Manufacturers

The National Academies of Science, Engineering and Medicine (NASEM) has published a report on resiliency in the medical supply chain that calls for the US Food and Drug Administration (FDA) to publicly disclose the location of all manufacturing facilities that supply ingredients and parts for pharmaceuticals and medical devices approved in the US.

The report recommends FDA publicly disclose information on drug sourcing, manufacturing quality and volume, and capacity for medical products approved for sale in the US.
 
“The manufacturer for a pharmaceutical drug should be required to publicly disclose the manufacturing location, in particular the FDA Establishment Identifier (FEI), the city, and the country for the finished dosage form (FDF), active pharmaceutical ingredient (API, major excipients, and major packaging and delivery devices for all pharmaceutical drugs sold in the United States,” said a report summary.
 
The same recommendation also applies to devices; device manufacturers should publicly disclose the manufacturing location in the FEI, the city, and the country involved in the device’s manufacturing and final assembly.
 
The report also recommends FDA make its risk-based site selection model scores publicly available. Wow, not only would that be good for consumers, I’d love to know where my sites fall in on that scoring.

Hurry up and put this recommendation in place!

Transparency is a good thing and it is shown to increase consumer safety. It is a problem that even a fairly knowledgeable industry professional like myself cannot figure out where generics are manufactured without making a few phone calls and shaking down my friend network. And even then, I’m never positive that I understand where my family’s medicine is coming from and the status of the sites involved in manufacturing and distributing the product.

Guidances in Administrative Law

Edward Rubin over on the Administrative Law JOTWELL, in the post “Uncovering the Hidden World of Administrative Guidance” exposed me to the 2019 article by Nicholas R. Parrillo “Federal Agency Guidance and the Power to Bind: An Empirical Study of Agencies and Industries” which I just find fascinating.

Guidances are an interesting part of our job. As a best practice, they show one way to get to the desired end result, but there can be other ways but the presence of guidance can obscure those possibilities. Often times if an agency goes to the level of detail to show you what good looks like you’d be foolish not to try to meet them there. Other times guidance can be a real head scratcher.

Good article, and of interest to the non-lawyers like myself who have to live within the boundaries.

Similac Recall is a Systematic Failure in our Food/Drug Safety

There has been a lot of press lately for the Abbott Nutrition recall of infant formula. Fundamentally this is a colossal failure of our regulatory program, another failure in a long string of failures, and confirmation that the time is now for radical changes in the agency.

Consumer Reports, in the article “How the FDA Bungled the Powdered Infant Formula Recall” does a good job covering the important points, so please read that article.

The optimist in me hopes that this calamity will drive needed change, as has been the unfortunate history of regulatory change in this country. I’m just not sure I hold enough confidence in Congress to get the job done.

Regulatory Requirements for Contamination Control

A list of Regulatory documents that apply to contamination control.

  1. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Chapter 3: Premises and Equipment, (2014)
  2. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Chapter 5: Production, (2014)
  3. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Part II: Basic Requirements for Active Substances used as Starting Materials, (2014)
  4. European Union, Guidelines of 19 March 2015 on the formalized risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use, Official Journal of the European Union, (2015/C 95/02), (2015)
  5. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Annex 2: Manufacture of Biological active substances and Medicinal Products for Human Use, (2018)
  6. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Annex 3 Manufacture of Radiopharmaceuticals, (2008)
  7. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Annex 14 Manufacture of Medicinal Products Derived from Human Blood or Plasma, (2011)
  8. European Commission, EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines, Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, (2017)
  9. European Union, Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use, Official Journal of the European Union, (2013/C 343/01), (2013),
  10. European Union, Guidelines of 19 March 2015 on principles of Good Distribution Practice of active substances for medicinal products for human use, Official Journal of the European Union, (2015/C 95/01), (2015)
  11. EMA Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (20 November 2014)
  12. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, subpart C = Building and Facilities, sec. 211.42 Design and construction features (b), (c)
  13. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, Subpart F – Production and Process Controls, sec. 211.113 Control of microbial contamination (a), (b)
  14. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, Subpart B – Organization and Personnel, sec.211.28 Personnel responsibilities (a)
  15. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, Subpart E – Control of Components and Drug Product Containers and Closures, sec. 211.80 General requirements. (b)
  16. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, Subpart E – Control of Components and Drug Product Containers and Closures, sec. 211.84 Testing and approval or rejection of components, drug product containers, and closures (d)
  17. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, Subpart D – Equipment, sec. 211.67 Equipment cleaning and maintenance (a)
  18. U.S. Food & Drug Administration, Code of Federal Regulation Title 21, part 211 current good manufacturing practice for finished pharmaceuticals, Subpart C – Buildings and Facilities, sec. 211.56 Sanitation (c)
  19. U.S. Food & Drug Administration, Guidance for Industry Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice, (2004)
  20. U.S. Food & Drug Administration, Guidance for Industry – Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing, (2020)
  21. U.S. Food & Drug Administration, Guidance for Industry – Guidance for Industry Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross Contamination, (2013)
  22. U.S. Food & Drug Administrationn, Guidance for Industry Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act, Draft Guidance. https://www.fda.gov/media/88905/download (accessed Mar 6, 2022)
  23. Pharmaceutical Inspection Co-operation Scheme gmp guide, 2nd targeted consultation document on revision of annex 1
  24. Pharmaceutical Inspection Co-operation Schemepharmaceutical inspection co-operation scheme gmp guide, ps inf 25 2019 (rev. 1) draft, manufacture of advanced therapy medicinal products for human use
  25. Pharmaceutical Inspection Co-operation Scheme gmp guide, ps inf 26 2019 (rev. 1) draft, manufacture of biological medicinal substances and products for human use
  26. Pharmaceutical Inspection Co-operation Scheme gmp guide, pe 009-15 (part i), guide to good manufacturing practice for medicinal products part i
  27. Pharmaceutical Inspection Co-operation Scheme gmp guide, pe 009-15 (part ii), guide to good manufacturing practice for medicinal products part ii
  28. Pharmaceutical Inspection Co-operation Scheme gmp guide, pe 009-15 (annexes), guide to good manufacturing practice for medicinal products annexes
  29. World Health Organisation, good manufacturing practices for pharmaceutical products: main principles, annex 2, who technical report series 986, 2014,
  30. World Health Organisation, who good manufacturing practices for active pharmaceutical ingredients (bulk drug substances), annex 2, who technical report series 957, 2010
  31. World Health Organisation, points to consider for manufacturers and inspectors: environmental aspects of manufacturing for the prevention of antimicrobial resistance annex 6, who technical report series 1025, 2020
  32. World Health Organisation, WHO good manufacturing practices for sterile pharmaceutical products, annex 6, who technical report series 961, 2011
  33. World Health Organisation, WHO good manufacturing practices for biological products, annex 3, who technical report series 996, 2016
  34. World Health Organisation, WHO good manufacturing practices for the manufacture of investigational pharmaceutical products for clinical trials in humans, annex 7, who technical report series 863, 1996
  35. World Health Organisation, WHO good manufacturing practices for radiopharmaceutical products annex 2, who technical report series 1025, 2020
  36. World Health Organisation, WHO GMP for Pharmaceutical Products containing Hazardous Substances, TRS 957, Annex-3 (2010)
  37. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use, Quality Risk Management, Q8 (R2), Pharmaceutical Development, August 2009. https://database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.pdf (Accessed Mar 06, 2022)
  38. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use, Quality Risk Management Q9, November. https://database.ich.org/sites/default/files/Q9%20Guideline.pdf (accessed Mar 06, 2022).
  39. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use, pharmaceutical quality system Q10. https://database.ich.org/sites/default/files/Q10%20Guideline.pdf (accessed Mar 06, 2022).