OhNo! and US cGMP Compliance

The Food and Drug Administration Modernization Act of 1997 directed the FDA to establish cGMP requirements for PET drugs. On December 10, 2009 the FDA established these requirements in 21 CFR Part 212. On December 12, 2011, compliance with the PET cGMP regulations will be required.

USP:  Until compliance with the new PET cGMP regulations is required, compounded PET drugs must comply with relevant USP monographs1. OhNo! can help - Click HERE for details.

cGMP:  The cGMP requirements for PET drugs were established by the FDA on December 10, 2009. Two years after that date on December 12, 2011, compliance with the PET cGMP regulations will be required2.
OhNo! can help - Click HERE  for details.

Electronic records:  OhNo! is not designed to create or use records required by predicate rules3 so it is exempt from the requirements of 21CFR11 “Electronic Records; Electronic Signatures”. Click HERE for details.

2nd Sight Solutions can not claim that its software is cGMP compliant or that it is “validated” (nor can any other software vendor).

According to FDA rules, compliance is the responsibility of the end-user and depends on installation, configuration, and operational decisions.

1. USP Monographs

The Modernization Act added a section of the Federal Food, Drug, and Cosmetic Act, which provides that a compounded PET drug is adulterated unless it is produced in compliance with USP compounding standards and official monographs for PET drugs. That section is to expire 2 years after the date on which the FDA establishes approval procedures and cGMP requirements for PET drugs. The USP general chapter on PET drug compounding, USP 29 <823> Radiopharmaceuticals for PET – Compounding  largely reflects the consensus views of the PET community and FDA on how to properly produce PET drugs. Until compliance with the PET cGMP regulations is required, the QA of compounded PET drug products must comply with relevant compounding standards and official monographs included in the USP.

2. FDA cGMP Rules

The Food and Drug Administration Modernization Act of 1997 directed FDA to establish cGMP requirements for PET drugs. On December 10, 2009 the FDA established these requirements in 21 CFR part 212 and published the rule and guidance:

Current Good Manufacturing Practice for Positron Emission Tomography Drugs” 
chapter 21 CFR Part 212

Guidance PET Drugs Products – Current Good Manufacturing Practice (cGMP)

3. Predicate Rules

Predicate rules describe the records that must be maintained for regulated activities such as PET drug manufacturing. A complete list of predicate rules for FDG manufacturing can be found in the cGMP regulations 21CFR212 (see above).

Of particular interest for new or small labs is the discussion of paper vs. electronic records. The FDA does not state a preference and does not recommend one strategy over the other. The difference is that systems based on paper storage are simpler, cheaper and easier to set up and maintain.

Typical paper storage methods include notebooks for incoming raw materials and ring binders for recording cleaning, maintenance, and stock inspections. Forms are usually printed from the computer before the activity begins. Data is entered by hand and initialed or signed. Storage does not have to be elegant or fast as long as the records can be produced if requested by auditors. Offsite storage is common.

Records can be kept electronically too - but the regulations covering them are rather more complex. They are described in 21CFR11 Electronic Records: Electronic Signatures. The FDA withdrew 21CF11 in 2003 because it was too expensive and difficult to implement and maintain. A new version is expected imminently, but in the meantime the old rules are still enforced, but using "discretion".

At a minimum, electronic record keeping requires:

  • Records must be secure, tamper proof and non-repudiateable.

  • Access to the computer must be limited to authorized individuals only.

  • The hardware and software configuration and version must be regularly checked

  • An audit trail must track all changes.

  • And many other requirements too.

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