Vaccine GMP Reevaluation Needed, NVAC Draft Report On Shortages Says

Good manufacturing practices for vaccines should be reevaluated in light of recent vaccine shortages, according to a National Vaccine Advisory Committee draft report.

A review of the implementation of good manufacturing standards for vaccines should be undertaken, "so that they do not have a material negative impact on supply," the report says.

"The review should ensure science-based regulatory processes and decisions."

"GMP needs to be dynamic with changes that incorporate technological advances and maintain or improve facilities to current standards but allow sufficient flexibility to ensure continued vaccine production," the draft report says.

Questions to be answered include: "How do the regulatory guidelines for vaccines differ from those for drugs and pharmaceutical agents? Should vaccines and biologics be regulated differently from drugs? Do current policies and practices for vaccines create possible impediments to an adequate supply of safe and effective vaccines?"

The draft report lists GMP oversight as a factor contributing to vaccine shortages, citing "application of systems and controls...that were not previously required." However, FDA rejected this idea at the June NVAC meeting. The statement is expected to be removed in the final version of the report.

The draft also suggests that unused vaccine should be the responsibility of the federal government to help mitigate the risks associated with a national stockpile.

While stockpiling vaccine would be the most effective strategy to alleviate short-term shortages, it is associated with inherent risks, the report states. "Even though vaccines in the inventory are to be stored temporarily and then rotated out to be sold in the market, it is likely that some of the vaccine likely will become out-of-date."

"The government needs to assume the risk of unused vaccine or vaccine for which there is no demand," the working group suggests.

The draft report was compiled by a 16-member NVAC working group on strengthening vaccine supply and was presented during the committee's June 4-5 meeting. The report has been sent back to the full committee for final comments, which are due June 18.

The final report will be submitted to HHS for budget considerations. HHS Assistant Secretary for Health Eve Slater, MD, urged submission of the document "as soon as possible" during the workgroup's April 1 conference call (¹ (Also see "Vaccine Stockpile Strategy Cost Implications Should Be Considered – NVAC" - Pink Sheet, 8 Apr, 2002.), p. 31).

Recommendations from the report could be discussed at a Senate Government Affairs Committee hearing on shortages of childhood vaccines June 12.

National Immunization Program Director Walter Orenstein, MD, is expected to testify at the hearing on factors contributing to the vaccine supply restraints, projections on shortage relief, and Centers for Disease Control & Prevention contracts. Acting FDA Commissioner Lester Crawford, PhD, will also testify on Orenstein's panel.

A second panel consists of Greater Baltimore Medical Center Pediatrics Chairman Timothy Doran, MD, (representing the American Academy of Pediatrics); Children's Mercy Hospitals & Clinics Chief-Pediatric Infectious Disease Mary Anne Jackson, MD; and Pharmaceutical Research & Manufacturers of America rep Aventis-Pasteur Exec VP Wayne Pisano.

Jackson and Doran will present clinical perspectives on the impact of vaccine shortages on immunization practices and vaccine-preventable disease. Pisano's testimony will likely emphasize the recent improvement in the supply of tetanus toxoid and diphtheria acellular pertussis vaccine, following the May 14 approval of Aventis' Daptacel .

Aventis is touting the addition of Daptacel to the DTaP market as a significant factor in alleviating shortages. Aventis anticipates to fill all public-sector DTaP orders by the third quarter (² (Also see "Aventis Daptacel Ordering Will Begin For Existing DTaP Customers May 28" - Pink Sheet, 20 May, 2002.), p. 35).

The supply of several routine childhood vaccines is improving, NVPO Associate Director Stephen Sepe told a June 6 meeting of the Advisory Commission on Childhood Vaccines. The NIP projects a return to full dosing of DTaP, tetanus-diphtheria and MMR vaccine within 30-90 days, and normal supply of Merck's varicella vaccine Varivax by August.

Regarding hepatitis B vaccine supply, "we are still expecting long delays for Merck and Wyeth, but Aventis-Pasteur, we are not expecting delays," Sepe said. "Pneumococcal conjugate vaccine remains in very short supply, with shortages in every state and among most providers. And it's difficult to reliably predict the date of return to" normal supply.

Influenza vaccine should not be stockpiled, since new product must be created each year, the report says.

A preparedness plan for an influenza pandemic has been presented to Slater, and briefings with HHS Secretary Tommy Thompson and Deputy Secretary Claude Allen are in the works.

Financial incentives, such as tax relief for new or renovated facilities and guaranteed pricing, could be used to alleviate supply problems, the draft report says. Government contracts that reward performance based on consistent and predictable vaccine delivery also could be developed.

Development of government owned or operated facilities should be avoided, however, since it could serve as a disincentive for industry and hinder long-term production goals, the NVAC group says.

Industry has voiced opposition to a government-owned facility, and Orenstein told the Senate Health Committee last year that a national vaccine facility would not solve near-term supply problems (³ (Also see "National Vaccine Facility Would Not Solve Current Shortages, CDC Says" - Pink Sheet, 3 Dec, 2001.), p. 6).

Determination of "appropriate incentives" for manufacturers to sustain supply and develop new vaccines could be accomplished by an "independent, multi-disciplinary group under the auspices of the Institute of Medicine," the working group suggests.

Streamlining the regulatory process for vaccine licensure is detailed in the report as an important focal point for resolving supply problems.

The NVAC group recommends "early and frequent communication with sponsors; regulatory research that facilitates product development; and fast track and accelerated approval programs."

While the report notes that legislation such as the Prescription Drug User Fee Act has provisions to expedite the review process, a study should be carried out to examine whether the intent of those provisions has been met and if additional legislation is needed.

Other recommendations include increased funding for the Center for Biologics Evaluation & Research, mutual recognition of lot release tests with other regulatory agencies and improved agency transparency of information to the public.