Lilly believes Zyprexa IM is on track for a late summer launch following receipt of an "approvable" letter from FDA.

The agency designated the intramuscular formulation of the antipsychotic agent olanzapine "approvable" March 29, two weeks after meeting with Lilly to discuss good manufacturing practices compliance issues raised during a preapproval inspection.

Lilly received a March 2 warning letter from the inspection of Building 105 in Indianapolis (¹ Also see "Zyprexa IM Manufacturing Issues To Be Discussed By FDA, Lilly March 15" - Pink Sheet, 12 March, 2001.).

The company filed the Zyprexa IM NDA (21-253) in June 2000, setting a user fee deadline in either April (10-month standard review) or June (12-month review).

While manufacturing issues are presumably among the items cited in the "approvable" letter, there also may be some labeling negotiation to complete.

FDA's Psychopharmacological Drugs Advisory Committee recommended Feb. 14 that the IM indication be limited specifically to the patient populations studied (schizophrenia, bipolar I disorder, dementia), rather than the general agitation claim sought by Lilly (² Also see "Lilly Zyprexa IM Agitation Use Should Be Limited To Patients Studied In Trials" - Pink Sheet, 19 February, 2001.).

The "approvable" designation for Zyprexa IM may be the first sign of a tangible impact from FDA's GMP concerns.

Lilly is in a tight race with Pfizer to launch the first injectable formulation of an "atypical" antipsychotic. If Zyprexa IM is significantly delayed by the manufacturing issues, Pfizer could have a window to establish Geodon IM (ziprasidone) in the acute care market.

Lilly also received an FD 483 report April 5 after a preapproval inspection of the manufacturing process for the osteoporosis agent Forteo (teriparatide) made at Lilly's Building 358 in Indianapolis.

FDA's observations following the Forteo inspection included concerns about quality control, validation, computer monitoring, operating and control systems, quality control functions, and water systems, Lilly said.

Lilly indicated that it could receive a second warning letter as a result of the Forteo inspection. The company continues to anticipate a fourth quarter launch for Forteo.

Lilly will have a chance to gauge investors' level of concern with the GMP issues during its quarterly earnings conference, scheduled for April 16. When the company disclosed the March 2 warning letter, it reassured investors that it did not anticipate a material financial impact.

Lilly's highest-profile pending application, for the anti-sepsis agent Zovant, is unlikely to be affected by the GMP issues in Indianapolis. The agent is manufactured for Lilly by Lonza.

Lilly is working with three consulting firms to help address concerns raised by FDA during pre-approval inspections for Forteo and Zyprexa IM.

AAC Consulting, Agallaco & Associates, and KMI will work with the company to implement a comprehensive action plan throughout Lilly's FDA-inspected facilities. The firms will perform mock-inspections to ensure Lilly is prepared for re-inspections of its Indianapolis sites.

In addition, Lilly plans to create a senior position to "focus on the development and implementation of a more robust approach for revalidation and requalification across our parenteral facilities," Lilly said in a March 8 response to FDA. The consultants will also assist in the evaluation.

AAC Consulting recently worked with Schering-Plough, conducting an external audit of the company's Kenilworth, N.J. facility in advance of an FDA preapproval inspection for Clarinex.

Selected findings of the Schering audit were released by Public Citizen in a letter to HHS demanding a criminal investigation of Schering-Plough's manufacturing compliance difficulties (³ Also see "Claritin Supply Sufficient For Spring, Schering Says; FDA Lists GMP Problems" - Pink Sheet, 5 March, 2001.).

FDA continues to take steps to keep its concerns about Lilly's GMP status in public view. The agency has posted its correspondence with Lilly on its website, citing numerous Freedom of Information requests.

Lilly Zyprexa IM "Approvable"; GMP Consultants Hired In Wake Of Inspections

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