In Brief: FDA Fights for Access; ARI Idled; ICH, PIC/S and EU Launch Initiatives

What happens now when plants block FDA inspections; how ARI drug shortage collaboration is falling short; how ICH is reforming; what PIC/S deems a deficiency; and how EU is updating the role of the QP.

FDA Uses New Powers against Firms that Deny, Delay or Limit Inspections

FDA has demonstrated how it will use new authorities granted last year by the FDA Safety and Innovation Act to compel drug makers to allow full access for inspections.

The Food Drug & Cosmetic Act already subjected plant personnel to criminal penalties for refusing access. The FDASIA revision allows FDA to also deem any drug made in such a plant as “adulterated.”

A July 12 draft guidance document shows FDA’s current thinking on what constitutes delaying, denying or limiting an inspection, and gave examples of some of the more common scenarios, such as refusal to schedule pre-announced inspections, temporarily withholding access to certain areas, leaving investigators to stew in conference rooms, falsely claiming the plant does not make pharmaceuticals, halting manufacturing activity to prevent direct observation of the manufacturing process, or failing to unlock or answer the door.

A July 18 FDA warning letter asserts that all products made at Wockhardt Ltd.’s plant in Aurangabad, India, are adulterated under the new FDASIA provision because the company delayed and limited a March 18-22 inspection. For example:

• A quality assurance officer initially failed to retrieve all the torn raw data records from the waste area that the investigator requested (these unofficial records showed batches failed to meet specs for visual inspection defect rates, contradicting official records);
• Asked to describe the contents of unlabelled and partially labeled vials, a quality control analyst instead began dumping them into the sink;
• The head of production denied the existence of unofficial batch record visual inspection results, except for one or two batches, but later recanted, having been contradicted by two manufacturing operators;
• Plant personnel prevented the investigator from observing operations on an aseptic filling line for more than an “unreasonably short” period of time;
• The plant did not provide a QC data package and raw testing documentation until the March 22 closeout meeting even though the investigator had requested it six times on March 20 and several times on March 21.

Accelerated Initiative Stuck in Neutral

The Accelerated Recovery Initiative has not yet been able to help alleviate drug shortages because it hasn’t identified situations where the new pilot collaboration could be of any added value, David Gaugh, Generic Pharmaceutical Association senior VP of sciences and regulatory affairs, said at the recent Drug Information Association annual meeting.

The initiative, a collaboration between GPhA, IMS Health Inc. and FDA to address drug shortage issues, is “struggling” because there are limited numbers of shortage drugs where there are three of four companies that could be called to help pick up the manufacturing needs, Gaugh said. Thus far, ARI hasn’t identified any shortage situations where it “can go the final step” and “help ramp up production,” he said (Also see "Generic Rx Shortage Initiative Stuck: Too Few Manufacturers To Pick Up Slack" - Pink Sheet, 8 Jul, 2013.).

ICH Reforms Continue

The International Conference on Harmonization said it made additional progress on becoming more transparent and more globally governed at its June 1-6 meeting in La Hulpe, Belgium.

ICH will publish more information about its doings and has integrated its Global Cooperation Group into sessions of its Steering Committee (Also see "ICH Enhances Regulators’ Roles While Preserving Industry Access" - Pink Sheet, 26 Jul, 2012.).

In other news, an ICH working group reached agreement on Q3D standards for elemental impurities to propose for comment (Also see "Pharma Gets More Time to Control Elemental Impurities" - Pink Sheet, 30 Aug, 2012.) (Also see "As ICH Q3D Metal Impurity Limits Near, Industry Worries What New Tests May Find" - Pink Sheet, 26 Apr, 2012.).

PIC/S to Harmonize GMP Deficiencies

The Pharmaceutical Inspection Cooperation Scheme said June 17 it established a working group at its May 28-30 meeting in Geneva to harmonize the classification of GMP deficiencies internationally and reach agreement on the top GMP deficiencies. Australia's Therapeutic Goods Administration will coordinate the effort.

EU GMP Annex 16 Revision Proposed

The European Commission July 5 launched a public consultation on a draft revision of Annex 16 of the European Union's GMP guidelines. The annex concerns certification by qualified persons and batch release. Comments are due by Nov. 5, e-mailed to: [email protected] and [email protected].