# Presentation: 180576

## The President’s Emergency Plan for AIDS Relief : Expediting Access and Ensuring Quality

**USPHS Scientific and Training Symposium**
**Pharmacy Category—Tuesday, June 5, 2007**
**CAPT Justina A. Molzon, M.S. Pharm., J.D.**
- Associate Director for International Programs
- Center for Drug Evaluation and Research
- U.S. Food and Drug Administration

## Adults and Children Estimated to Be Living with HIV in 2006

*Adults and Children Estimated to Be Living with HIV **in 2006*

- Source: UNAIDS, 2006

## President’s Emergency Plan For AIDS Relief

- Announced January 2003, operating by 2004
- “2-7-10” goals in five years
- Treatment of _2 million_ HIV-infected people
- Prevention of _7 million_ new infections
- Care for _10 million_ people infected with and affected by HIV/AIDS, including orphans and vulnerable children
- New leadership model:  US Global AIDS Coordinator, inter-agency teams with Ambassador-level leadership in-country
- Current US Global AIDS Coordinator*—*CAPT Mark Dybul, USPHS
- Adherence to country-level national AIDS plan, which includes in-country coordination with Global Fund and other donors

## PEPFAR Focus Countries

- PEPFAR works predominately in 15 focus countries.
- Account for nearly 20 million HIV-infected men, women and children--almost 70 percent of the total in all of Africa and the Caribbean and 50 percent of global HIV infections
- These countries were selected because, with PEPFAR support, they should be able to achieve national scale-up of HIV/AIDS prevention, treatment and care by 2009
- 15 countries Botswana, Cote d’Ivoire, Ethiopia, Guyana, Haiti, Kenya, Mozambique, Namibia, Nigeria, Rwanda, South Africa, Tanzania, Uganda, Vietnam and Zambia

## PEPFAR Focus Countries

*PEPFAR Focus Countries*

## Meeting Treatment Goals

- Successful implementation of PEPFAR’s treatment goals requires unprecedented amounts of safe, effective, and lower cost antiretroviral drugs (ARVs)
- To meet these goals, in May of 2004 the US Food and Drug Administration (FDA) announced and implemented an expedited review process for fixed dose combination ARVs
- ARVs approved or tentatively approved by FDA under this process meet all FDA standards for safety, efficacy, quality, and manufacturing and are eligible for purchase with PEPFAR funds

## FDA Guidance to Promote FDCs 

*Draft Guidance for Industry—Fixed Dose Combination and Co-Packaged Drug Products for Treatment of HIV—Posted* May 17, 2004
- Guidance was built upon a principles document adopted at a Conference held in Gabarone, Botswana in March of 2004 and cosponsored by the:
- US Department of Health and Human Services (HHS)
- Joint United Nations Program on HIV/AIDS (UNAIDS)
- World Health Organization (WHO)
- Southern African Development Community (SADC)
- Outlines four scenarios for review of different FDC and co-packaged products
- Some of the scenarios could permit approval or tentative approval in as little as two to six weeks after submission of a high-quality marketing application
- Final guidance issued in October 2006 based on experience with submissions to date
- http://www.fda.gov/cder/guidance/6360fnl.pdf

## Product Application Review

- The FDA expedited review process applies to individual ARV drug formulations, co-packaging of individual drug formulations, and fixed-dose combinations (FDCs)
- This unique mechanism ensures that ARVs purchased by PEPFAR meet the same safety, efficacy, and manufacturing quality standards as drugs used in the US
- For generic ARVs that can be marketed in the U.S***., ****full* *approval* is granted
- For those that cannot be marketed in the U.S. due to existing patent protection, *tentative approval* is granted

## Tentative Approval

- A US FDA tentative approval indicates:
- That the technical/scientific requirements for approval have been met
- That the product is bioequivalent to the reference listed drug
- That the firm is in compliance with the U.S. Food and Drug Administration’s current good manufacturing practices (cGMPs),
- In addition, the applicant has generally utilized the recommendations listed in the *Guidance to Industry: Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV  *
- FINAL Guidance issued October 17, 2006
- However, the approval for distribution in the United States of America cannot be made effective until the expiration of the patents and/or period of marketing exclusivity
- An antiretroviral receiving a tentative approval is eligible for purchase with the PEPFAR funds as it has met US FDA standards for safety, efficacy and quality

## Encouraging Participation

- FDA has actively encouraged sponsors worldwide to submit US marketing applications for single entity, fixed dose combination (FDC) and co-packaged versions of previously approved ARV therapies
- Submissions were encouraged even if there was still patent or exclusivity market protection for the product in the US

## FDA PEPFAR ARVs Approvals/Tentative Approvals

*FDA PEPFAR ARVs **Approvals/Tentative Approvals*

- May 15, 2007

## Antiretrovirals Associated with PEPFAR Expedited Review Process

- 43 antiretrovirals currently listed
- http://www.fda.gov/oia/pepfar.htm
-  6 Approved products
- 37 Tentatively approved products
- 4 of the approved products switched from tentatively approved to approved upon expiration of the patent

## Engaged Drug Regulatory Authorities 

- FDA has proactively engaged with its counterpart regulatory agencies in the 15  PEPFAR focus countries
- Promote understanding of the initiative and the science behind FDA’s regulatory decisions
- Promote utilization of FDA’s efforts in local registration of products in focus countries and use by their citizens
- September 2005--focus country drug regulatory authorities participated in a Forum on FDA’s expedited review process

## Collaboration with WHO

- In August of 2005 the FDA signed a confidentiality agreement with the Quality Assurance and Safety Medicines Unit of WHO responsible for its prequalification program for antiretrovirals
- This allows FDA approved/tentatively approved ARV’s to be included among WHO’s *prequalified* products
- It is expected that recognition of the safety, efficacy, and manufacturing quality of these generic ARVs by both FDA and WHO will lead to their greatest use in countries served by PEPFAR programs

## WHO/QSM  Procurement, Quality and Sourcing Project

- Prequalified list of manufacturers and suppliers whose HIV-related medicines have been found acceptable, in principle, for procurement by UN agencies
- WHO has agreed to list FDA’s approved or tentatively approved products on this prequalification list

## WHO Prequalification List-Footnote

- 	The products listed with the note "USFDA" have been added to the list of products prequalified by WHO, relying on the scientific assessment and inspections conducted by the USFDA and based on the exchange of relevant information between the USFDA and WHO in accordance with a confidentiality arrangement between the two organizations

## WHO Prequalification List-Footnote

- Where a product has been listed with the indication "tentatively approved", this means that although existing patents and/or other legal marketing exclusivity prevent marketing
- 	this specific company's product in the USA, **the product meets all of the USFDA's safety, efficacy, and manufacturing quality standards required for marketing in the USA**
- Upon expiry of patent protection in the USA, tentatively approved products will be authorized for marketing in the USA

## ARVs Available for PEPFAR purchase (thru 5/15/2007) 

- 30 single-dose ARV formulations
- 13 FDCs
- 3 triple-drug FDCs,
- 10 dual-drug FDCs,
- 5 are co-packaged with a third drug
- 8 ARVs in formulations suitable for children
-  List at:   http://www.fda.gov/oia/pepfar.htm

## Increased Availability of ARVs

- FDA’s expedited review has increased the availability of safe, effective, low-cost generic ARVs in the developing world
- As a side benefit, the process has also expedited the availability in the US of six generic versions of ARVs whose US patent protection has expired
- Increased availability of generic ARVs eligible for purchase with PEPFAR funds has helped lower the cost of these products

## Significant Cost Savings for ARVs

- FDA approval of generic ARVs can provide cost savings
- The purchase of Didanosine 200 mg and Efavirenz 200mg, two generic drugs recently approved/tentatively approved  by US FDA, resulted in cost savings for SCMS of more than $46,000 (53 percent) and $116,000 (52 percent) respectively, compared with the Accelerated Access Initiative (AAI) Unit Price(1).
- Buying generic ARVs results in significant cost savings
- 88 percent of ARVs (by volume) purchased by SCMS from January to March 2007 were generics, compared with 72 percent from April to September 2006
- From January to March 2007, SCMS saved more than $30 million (70 percent) by buying generics, comparing the SCMS generic price achieved to AAI Unit Pricing. The savings from October to December 2006 were $19.8 million (59 percent)
* **The amount saved was greatly influenced by the purchase of the generic version of Nevirapine 200mg, which contributed more than $12 million to the total savings from January to March 2007 and $6 million from October to December 2006.*

*(1) The Accelerated Access Initiative is a program of the World Health Organization (WHO) in partnership with six research-based pharmaceutical companies to provide developing countries access to branded ARV medicines at heavily discounted prices.*

## Lowering the cost of antiretroviral medicines enable programs to extend life-saving treatment to more men, women and children.

- Ambassador Mark Dybul, US Global AIDS Coordinator Testimony before the House Committee on Foreign Affairs
-  Washington, DC--April 24, 2007
- CAPT USPHS

## Challenges

- Challenges remain due to technical and resource limitations on the part of some national drug regulatory authorities, possibly leading to lengthy times for review, approval, and importation of these generic ARVs
-  As a result, PEPFAR cost savings from generic ARVs may not be realized in these countries

## Key Recommendations

- Treatment implementers and commodities procurement organizations should follow the list of FDA generic ARV approvals at http://www.fda.gov/oia/pepfar.htm and share information about these drugs with in-country drug regulatory authorities to encourage rapid local review and approval or waiver for importation of listed drugs that are needed in-country

## Key Recommendations

- In-country drug regulatory authorities should continue to strengthen their product review expertise to promote rapid in-country approval of ARVs
- Treatment implementers should build effective relationships with local drug regulatory authorities
- USFDA should continue to work with drug regulators, WHO, and the drug industry to promote selection of ARVs reviewed under it

##  By making these much-needed, high-quality generic antiretroviral products available for registration and marketing in the 15 PEPFAR focus countries, the USFDA has helped save lives and significantly reduced the cost of treatment

***The Power of Partnerships: ***
***Third Annual Report to Congress on PEPFAR  (2007) page 174***

## Helpful Websites

- PEPFAR
- http://www.pepfar.gov/
- Office of the U.S. Global Aids Coordinator
- http://www.state.gov/s/gac/
- Office of Global Health Affairs-- Department of U.S. Health and Human Services
- http://www.globalhealth.gov/
-  FDA approved and tentatively approved ARVs
- http://www.fda.gov/oia/pepfar.htm

## Thank you for your attention