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In This March 2015 Issue

Is your Cleaning program ready for your next EU inspection?
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"Are there any big differences between EU and US expectations for Cleaning Validation?"

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EU Legislation: EudraLex Volume 4 - Good Manufacturing Practice (GMP) Guidelines, Annex 15: Qualification and Validation final draft is in preparation and is set to be updated to include recommendations promoted by the ISPE document "Risk-Based Manufacture of Pharmaceutical Products" (Risk-MaPP - Volume 7 of Baseline Guides), covering the topic of Cleaning Validation. As a result, the following will be added to the Cleaning Validation section of Annex 15:

9.5--Limits for the carryover of product residues should be based on a toxicological evaluation to determine the product specific permitted daily exposure (PDE) value. The justification for the selected PDE value should be documented in a risk assessment which includes all the supporting references. The removal of any cleaning agents used should also be confirmed.

This has been a contentious and highly debated topic over the past several years as the Risk-MaPP includes statements that current methods of setting limits for actives are "not science-based", "arbitrary", lack support, and are misleading and wrong. The point of contention deals with the lack of clear distinction between "highly hazardous" actives and non-highly hazardous actives, and the elimination of the dose based criteria for setting maximum allowable carry over. The EU Guidance will be based strictly on a toxicity criteria for setting limits for carryover. Hence, in the future we may see the 0.001 of a dose criteria (which is the principal method used in the US for non-hazardous actives) to be considered non-compliant with EU-GMP.

In the case of non-hazardous (high dose) products, it will likely permit "higher" levels of Maximum Allowable Carryover then the 0.001 of a dose criteria which. However, only time will tell how US Regulators feel about this potential for a greatly relaxed target for cleaning.

Ultimately, this is a matter to be aware of and to have provisions for in your Cleaning Programs. Ongoing assessments and life cycle management of your Cleaning Programs should designed to capture all available Toxicology information for your products so that you can see how the Maximum Allowable Carryover (MAC) will be affected by this new consideration.

Dr. Daniel J. Hoch

Vice President, Protocol Link

New Guidance for Compounding Pharmacies 
On February 13th, the FDA released four draft guidances and a draft memorandum of understanding related to drug compounding and repackaging that are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians. These documents are the most recent in a series of guidance documents issued by the FDA as part of its implementation of the Drug Quality and Security Act, which was enacted in November 2013.

The new draft guidance documents address the following four topics: whether to register as a 503B outsourcing facility; drug repackaging by pharmacies and outsourcing facilities; mixing, diluting, and repackaging biological products without an approved BLA; and adverse event reporting for 503B outsourcing facilities. The draft memorandum of understanding describes the responsibilities of a state to investigate complaints related to compounded drug products distributed outside the state and to address facilities whose interstate distribution of compounded drug products is "inordinate."

See FDA's press release for a link to all five documents, along with brief descriptions of each. Please contact Matt Daly for more information on this topic.
A Word From Our Staff
Scott Buckely is a Project Manager for Protocol Link with experience in the areas of program management, quality systems, design controls, digital marketing, ERP management, technical writing, and personnel training. Mr. Buckely received his MBA from Northern Illinois University and his B.B. from Western Illinois University.

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"Running an effective meeting is key to successfully delivering projects, and not as simple as you think."

Tip 1: Establish expectations by preparing an agenda. If you don't need an agenda, you don't need a meeting.

 

Tip 2: Schedule meeting durations that match the agenda; avoid scheduling a 60 minute meeting if you only need 45.

Bonus Tip: Having trouble starting your meetings on-time due to late attendees? Change your 60 minute meeting to 45 minutes and have it start 15 minutes later. This will allow for a "passing period" and meeting participants can join on time even if the previous meeting runs over.

 

Tip 3: Include the minimum number of participants and/or functions. This helps avoid getting off topic and the need to take conversations "offline."

Bonus Tip: If someone doesn't participate during the meeting they don't need to attend. If they want to stay informed they can review the summary after the meeting.

 

Tip 4: Document the meeting attendees, discussion points, action items and due dates. This helps with accountability and hitting target dates.
Scott Buckely
Project Manager, Protocol Link
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