There are several concepts embedded in this question and therefore in order to answer it, it must be broken down into several parts. On the basis of the question being asked, the chart below shows a depiction of the two possible outcomes of e-documents that may be included in NDA or ANDA and / or are subsequently used for technology transfer to commercial production. While on the surface, the two outcomes of e-documents used to communicate a manufacturers product and process lifecycle controls in an NDA, NDA filing or used for technology transfer to commercial production appear to be for different purposes, in reality, they are not all that very different from each other based on the new rules that have been written by the FDA and the EU. Those same e-documents may be used to communicate the same product and process lifecycle controls information for commercial production, be it to an internal division via a filing / technical transfer or to an external outsourced contract manufacturer via a quality agreement / technical transfer. As they say, the devil is in the details. As we shall see shortly, the FDA and the EU have grabbed the devil by his horns and have addressed those details.

Currently there are several high level regulatory documents that are being used to drive industry best practices for E documentation globally; ICH Q7A (for API), Q11 for finished product (FP) and the EU Annex 11.

The question further demands whether or not e-documents originally filed in an ANDA or NDA and / or subsequently used for technology transfer to commercial production are R&D documents simply versioned and/or reclassified as they undergo approvals by QA and are transferred to production? The answer may surprise you, but how these documents flow is really dependent upon two major pieces of regulations that both the FDA and EU use in slightly different ways but in the end, both achieve the desired result of controlling quality of the manufactured API or product. Those are the quality management systems regulations primarily embedded in ICH Q10 (but other elements of critical importance are also cited in Q8, Q9 and Q11) and in Chapter 1 of the EU-GMP Guide, which is now referred to as "Pharmaceutical Quality System.”

The short answer then is that e-documents must follow a lifecycle that, in the context of an ANDA or NDA filing in the US, or market authorization in the EU adequately describe risk throughout the lifecycle of the process as understanding increases. This concept may be applied to small molecules as well as large molecules and to human as well as to veterinary drugs also. The long answer is that the FDA and the EU have been gearing up for these changes for some time as mounting pressures for greater regulatory scrutiny have come about as generics have taken on a larger share of the market as they compete with branded products and as biosimilars are on the verge to appear in the market as well. While all of this is playing out in the market, the regulators have had to essentially, rethink and redesign what qualities are important to control and monitor during the drug and product lifecycle with respect to safety and efficacy, and who to regulate with more intensity for those who dare to compromise their processes and provide more flexibility for those who are innovating and have led the way towards the holy grail of individualized medicines.

Furthermore, it may come to pass that as this response is being written, for the US anyway, the deadline for final comments to the draft Guidance for Industry Contract Manufacturing Arrangements for Drugs: Quality Agreements is looming around the corner and the impact that this guidance will have on e- documentation on outsourced manufacturing will be far reaching. Following the recent EU GMP revisions in January of 2013, the impact could be summarized simply by stating the following directly from the guidance itself:

“The Quality Agreement should indicate procedures for the Owner to review and approve documents and any changes thereto, such as Standard Operating Procedures, manufacturing records, specifications, laboratory records, validation documentation, investigation records, annual reports, and any other documents /records related to the product manufactured or services provided by the Contracted Facility.”

From an industry perspective, this should not be treated as cGMPs business as usual. Far from it, this is cGMPs on steroids! While the industry may need clarification on some of the finer points of the guidance such as defining “Owner”, their real focus should be on how a quality agreement will now operate in the newly created environment that gives the FDA far more powers than it has had in the past since the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law on July 9, 2012. Simply stated, as the pharmaceutical and biopharmaceutical industries have expanded globally, FDASIA has greatly expanded the FDA's authority and reach into new areas such as contract law that ultimately will have an increasingly significant impact on the “no longer made in the USA” drug quality as well as challenges within the multinational regulatory EU environment that has its own set of quality issues to contend with.

electronic documentation