Expanded Access for Treatment Use & Compassionate Use

1. Purpose

This policy sets forth Pfizer standards for compassionate use, including expanded access for treatment use, named patient and cohort programs, involving unapproved Pfizer investigational products outside a clinical study. Provision of unapproved investigational products to patients outside of a clinical trial is subject to this policy.

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2. Scope

This policy applies globally with respect to expanded access and compassionate use requests for investigational products with active ingredients that have not been approved for any purpose in the country from which the request originates, or are otherwise not available in that country through normal commercial channels. For purposes of this policy, an expanded access or compassionate use request is any request for the use of an investigational product outside the scope of a clinical study.

Pfizer development resources are focused on conducting clinical studies and obtaining regulatory approval of investigational products. Pfizer is also committed to making reasonable accommodations so that seriously ill patients who have exhausted other appropriate treatment options may, under the conditions described in this policy and in accordance with applicable local law, have appropriate access to investigational products before they are commercially available.

This policy generally does not cover requests for unapproved new dosage form versions of a commercially available product (e.g., a request for an unapproved intravenous formulation of a product which is a solid oral dosage form which has already been approved). However, decisions relating to such requests are governed by the same considerations as those presented in this policy. Pfizer recognizes that in some cases, the risk/benefit analysis may favor expanded access or compassionate use of new formulations at an earlier stage of clinical development than would be the case for investigational products that have not been approved for any purpose. Accordingly, Pfizer evaluates expanded access and compassionate use requests for new formulations on a case-by-case basis.

Pfizer-sponsored clinical studies, open label safety studies, and continuation phases of clinical trials are out of scope of this policy. It is important to note that in the European Union (EU), the term 'expanded access program' generally refers to a program run as a clinical trial.

Expanded access and compassionate use studies cannot be considered unless the local regulations allow such programs. When they do, they must comply with the country-specific legal and regulatory requirements and therefore may differ among markets. For example, within the US, expanded access studies include treatment protocols or treatment use Investigational New Drug (INDs), and individual patient and multi-patient expanded access studies. In the EU, as permitted by Member States' national laws, compassionate use can take the form of named patient use and cohort programs.

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3. Policy

Pfizer considers expanded access and compassionate use requests only when all of the following criteria are met:

1. The investigational product is being studied under an appropriate regulatory authorization or all investigational studies of the product have been completed;
2. The patient(s) for whom expanded access or compassionate use is sought:
• Is suffering from a serious disease or condition;
• Has undergone appropriate standard treatments without success, no comparable or satisfactory alternative treatment is available or no standard treatment exists for the disease or condition;
• Is ineligible for participation in any ongoing clinical study of the investigational product; and
• Meets any other relevant medical criteria for compassionate use of the investigational product, as established by Pfizer.
3. There are meaningful human clinical data to support an assessment that the potential benefits to the patient outweigh the risks to the patient. In practice, this will generally occur at a point when Pfizer management has made a decision to seek marketing approval in one or more countries;
4. Providing the investigational product for expanded access or compassionate use will not interfere with development of the product;
5. The physician attending to the patient(s) for whom expanded access or compassionate use is sought agrees to comply with all applicable legal and regulatory requirements in relation to the request and any requirements in terms of medical criteria, safety reporting or other data provision which the relevant study team may require.

In general, where permitted by local regulation, expanded access or compassionate use treatment will be discontinued when the product becomes commercially available in that location.

If a patient does not have any possible access (e.g., due to geographic limitations) or if they have already failed to respond to the active comparator of a clinical trial with the unapproved product they may be considered for compassionate use on a case-by-case basis.

Study teams are required to review compassionate use requests on a fair and equitable basis in accordance with the principles set forth in this policy. When requests are granted (i.e., expanded access or compassionate use) relevant documentation (e.g., investigator brochure, labeling documentation, protocol) regarding the use and safety of investigational product must be provided to the treating physician.

Named patient use and single patient compassionate use do not generally require monitoring. Monitoring of other expanded access and compassionate use programs must be carried out where required by and in accordance with local law and regulation.

Certain expanded access and treatment studies, which involve the collection of safety and efficacy data, must be registered on the www.clinicaltrials.gov website (ClinicalTrials.gov) and the results of those studies disclosed by PhRMA results database at www.clinicalstudyresults.org as well as Basic Results posted on ClinicalTrials.gov in accordance with the Pfizer standards on public disclosure.

Below are overviews of compassionate use and expanded access programs in the US, and compassionate use in the EU.

3.1 US: Types of Expanded Access

Food and Drug Administration (FDA) allows expanded access to investigational products for treatment use where the condition is serious or life-threatening, there is no comparable or satisfactory treatment or therapy, the investigational product is under investigation (or all studies are completed), and the sponsor is pursuing marketing approval.

Regulatory requirements for Adverse Event (AE) reporting, informed consent, Institutional Review Board (IRB) review, maintenance of case histories and investigational product disposition records apply to US expanded access programs. The following three types of expanded access are recognized for the US:

3.1.1 Individual Patient (or Emergency Use)

Individual patient use may be used to provide treatment for individual patients where the treating physician has determined that the risk of treatment is not greater than the risk of disease/condition. The patient must not be eligible to get the investigational product under another IND or protocol. The duration of study is generally limited to a single course of treatment. Consultation with the IRB and or IRB chairperson is required.

3.1.2 Intermediate Size (<100) Patient Population Studies

Intermediate size studies may be used with small patient populations where there is enough evidence of safety of the investigational product at the dose and for the proposed duration of use and that there is at least preliminary clinical evidence of effectiveness. This may include situations where the investigational product is being developed or has been withdrawn, where enrollment is closed in the ongoing trials, or where patients are not eligible to participate in the trial (due to enrollment criteria or geographical location of the trial).

3.1.3 Expanded Access Under Treatment INDS and Treatment Protocols for Large Patient Populations

Expanded access protocols designed to treat a larger population of patients (generally > 100) with life threatening diseases who cannot participate in controlled clinical trials and for whom there are no satisfactory alternative therapies can be conducted using a Treatment IND or Treatment Protocol. These trials for large groups of patients are only conducted where there is reasonable evidence to support the efficacy and safety of the drug, generally based on the results of Phase III trials. Treatment INDs are not primarily intended to assess the efficacy or safety of the investigational product, but are intended to treat the patient.

3.2 European Union Compassionate Use

Compassionate use in the EU is as permitted in each Member State's national laws.

Reporting of adverse events (AEs) to the relevant competent authorities should be carried out by the treating physician(s) and Serious Adverse Events (SAEs) should also be notified to Pfizer. Other regulatory requirements such as informed consent, ethics committee review, vary according to Member State national laws.

3.2.1 Named Patient Use

The supply of an unauthorized product in response to a request of a healthcare professional for an individual patient having a special need for it, according to the judgment of and under the responsibility of the prescribing physician. This concept is recognized and such supply permitted (subject to varying conditions) under the national laws of almost all EU member states, pursuant to Article 5 of Directive 2001/83/EC.

3.2.2 Cohort Program Studies

The supply of unauthorized products to a pre-determined group of eligible patients, outside the scope of a clinical trial, in collaboration between Pfizer and interested physicians/hospitals, and subject to agreement with the relevant regulatory authority.

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4. Responsibilities

It is the responsibility of the study team, in conjunction with Medical, Regulatory Affairs and Legal representatives, to consider compassionate use requests that satisfy the criteria set forth in this policy. If the study team cannot reach a consensus, the final decision rests with the clinician/clinical lead.

Exceptions to this policy may be granted only after recommendation by the clinician/clinical lead and with written approval by appropriate senior management in consultation with Legal.

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