Our goal is to ensure that the data associated with drug manufacturing are complete, consistent, and accurate, and therefore reliable.
— Read on www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm628244.htm
In the last 6 years, Pfizer’s Hospira plant in Kansas has received eight FDA Form 483 citations, as well as other observations for regulatory bodies, such as this summer’s from the MHRA.
The latest FDA 483 was in August 2018.
On 30-Nov-2018 PIC/S published the third draft of guidance PI 041-1 “Good Practices for Data Management and Data Integrity in regulated GMP/GDP Environments“. The first draft was published back in 2016, and the third draft is subject to a focused stakeholder consultation seeking substantive comments from trade and professional associations on specific questions relating to the proportionality, clarity and implementation of the guidance requirements. In parallel to this stakeholder consultation, the new draft is applied by PIC/S Participating Authorities on a trial basis for a new implementation trial period (3 months).
In short, you can expect inspectors to have reviewed and be reviewing against this. Do your gap analysis now and have plans in place to address the gaps. Yes, there will be a little while before this is finally published, but at this point this guidance neatly triangulates with other guidances on data integrity and we can expect most of this to be in the final version.
This document is a great place to start and can be used to develop whole sections of the quality management system. I find it very actionable. For example this table from 9.5 “Data capture/entry for computerised systems”:
Significantly, your firm failed to perform identification testing for all incoming glycerin lots to verify identity and determine whether diethylene glycol (DEG) or ethylene glycol (EG) was present. Because you did not test each lot and container of glycerin using the USP identification test that detects these hazardous impurities, you failed to ensure the acceptability of component lots used in drug product manufacture. DEG contamination in pharmaceutical products has caused lethal poisoning incidents in humans worldwide.FDA Warning Letter of 02-Nov-2018 to Product Packaging West, Inc.
First of all, ouch. This brings to mind an old investigation that drew a lot of attention a few years back. It involved a tanker truck and a hurricane, but still, lots of memories.
This Warning Letter brings to mind questions about receipt of materials. So here are some top level thoughts.
Choosing tests should be a risk based approach evaluating what the material is, what it is used for, supplier qualification level and history of test results. A critical raw material with custom chemistry from a supplier that has had issues is a different matter than an off-the-shelf component that hasn’t had a problem in 10 years. But there always should some basic identity testing, especially if that is listed in an pharmacopeia. This should be done through a formal process, with periodic review.
Have a process in place for delivery of material to ensure that each container or grouping of containers of material are examined visually for correct labeling (including correlation between the name used by the supplier and the in-house name/code, if these are different), container damage, broken seals, and evidence of tampering or contamination. A good in-coming receipt inspection includes:
- Each lot within a shipment of material or components is assigned a distinctive code and an unique internal number so material or component can be traced through manufacturing and distribution
- A check to guarantee the origin of materials from approved manufacturers and approved distributors
- Start inspection with visual examination of each shipping container for appropriate labelling, signs of damage, or contamination
- Use a predefined checklist for inspection
Incoming material should be quarantined prior to approval for use. I recommend a separate quarantine area for incoming versus material segregated for investigations or issues.
Supplier qualification deserves a post of it’s own.
In light of recent criticism of FDA’s oversight of medical devices, it is curious why FDA did not release a report touting the success of its enforcement activities with the same fanfare as its report on its plan to modernize the 510(k) program, which we reported on here. The Medical Device Enforcement and Quality Report (Report), available here, claims FDA’s increased inspections have led to improved compliance by industry.
— Read on www.fdalawblog.net/2018/12/medical-device-enforcement-and-quality-report/
Last week the ICH published a reflection paper “Advancing Biopharmaceutical Quality Standards to Support Continual Improvement and Innovation in Manufacturing Technologies and Approaches.”
The ICH contines to move beyond the prescriptive guidances of Q1-7 and focus more on strengthening the conceptual framework of Q8-Q11 (see some of my thoughts here). There is a lot of talk about strengthening relationships and alignment between regulatory agencies, which is definitely needed. Q12 has had a bumpy road of it (EU saying they might not implement, US FDA issuing a guidance that’s not all that aligned). We see a firm commitment to continuing the QbD work with Q13 (continuous manufacturing) and Q14 (Analytical methods).
Interesting timing with the FDA recent announcement on generics.
Back in October, FDA announced that it submitted a proposal to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) for the development of common global standards for generic drugs.
— Read on www.fdalawblog.net/2018/11/international-plan-of-mystery-ich-guidelines-for-generic-drugs/
Interesting blog post on FDA’s thoughts on the ICH creating some standards on generics.