Can preview data be used for demonstrating compliance with regulatory authorities?

The short answer is NO. The primary purpose of the preview data is to help in the decision-making process of whether you can handle a product or not. Based on the guidance provided by the European Medicines Agency (EMA) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S), you need the full Health-Based Exposure Limit (HBEL) report or assessment document; merely having the Acceptable Daily Exposure (ADE) or Permitted Daily Exposure (PDE) value is not sufficient for compliance or sound quality risk management (QRM) practice

The EMA and PIC/S consider the ADE (or PDE) value as the critical numerical output, but the scientific rationale and underlying documentation that justifies this value are essential for regulatory acceptance and for correctly informing your facility's cross-contamination control strategy

Here is a detailed elaboration on why the complete HBEL assessment report is necessary:

1. The HBEL/PDE Value is Only the Starting Point.  The EMA and PIC/S require a documented Quality Risk Management process to determine if products can be safely manufactured in shared facilities. The HBEL, whether termed ADE or PDE (which are synonymous), is defined as the maximum substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed to it daily over a lifetime. This value serves as the scientifically justified threshold against which the likelihood and severity of cross-contamination risks are assessed. The guidelines emphasize that the process of determining controls should not simply involve setting a cleaning limit based on the final PDE value; instead, the entire rationale must be used in the QRM study to address potential exposure routes (mix-up, retention, airborne, mechanical transfer)
2. Mandatory Documentation and Rationale Requirements. The EMA Guideline on setting HBELs (which PIC/S adopted) explicitly outlines the stringent documentation required for the PDE determination strategy.
3. Scientific Rigor and Justification The full HBEL report must demonstrate the rigorous scientific basis for the final PDE number. This documentation is critical because HBELs are derived through a highly interpretative process involving extrapolation and the application of various adjustment factors (AFs).

1. Comprehensive Data Review: A review of all available animal and human pharmacological and toxicological data must be performed. The report must include a detailed scientific literature search, and the search strategy and the results must be clearly documented.

2. Expert Sign-off: The HBEL must be determined by a qualified expert (e.g., toxicologist or pharmacologist) who has expertise and experience in determining HBELs. The report must be signed, dated, and should include or reference the expert's Curriculum Vitae (CV). If the service is outsourced, the manufacturer must assess the suitability and competence of the provider.

3. Critical Effect Identification: The assessment must identify the critical effect(s)—the most sensitive adverse pharmacological or toxicological endpoint—and the Point of Departure (PoD) (e.g., the NOAEL or LOAEL) used for the calculation.

4. Adjustment Factors (AFs): The methodology must provide a clear rationale regarding the adjustment factors (F1 to F5) applied to account for uncertainties such as interspecies and intraspecies variability, study duration, and the nature of toxicity. Deviations from default factors must be scientifically justified.

5. Route of Administration (Extrapolation): The documentation must address the derivation of HBELs for all relevant routes of exposure, especially if extrapolation to other routes of administration (such as oral to inhalation) was necessary, potentially including bioavailability correction factors.

Regulatory Oversight

1. The PIC/S Aide-Memoire for inspectors confirms that a highly structured HBEL assessment report is required. Inspectors will review this documentation to ensure the HBEL value was derived correctly. If the manufacturer purchases a report, they are still responsible for recording an assessment of the HBEL document received to ensure suitability for their specific manufacturing context. Significant variations (at or above 10-fold) in HBEL values for the same substance must be investigated, underscoring why the scientific report is needed to justify the resulting number. Simply converting the HBEL into a cleaning limit and confirming detection capability is explicitly not considered a QRM approach.

Using the HBEL Report in Quality Risk Management (QRM)

The HBEL document is necessary to guide the subsequent QRM process, which relies on understanding the severity of the hazard to select appropriate controls

Commensurate Controls: The QRM study must be aligned with the level of the HBEL. Products posing a higher hazard (lower HBEL value) require more elaborate organizational and technical control measures

Risk Evaluation: The full report contains the context necessary to assess the risk of potential cross-contamination down to the established HBEL level, considering how easily that quantity of contamination could occur at both the batch and unit dose level.

Cleaning Limits: While the HBEL should be used to establish maximum safe carryover (MSC) and maximum safe surface residue (MSSR) values for cleaning, the report's underlying data is needed to confirm if analytical testing can meet the required detection limit, which may be far below the visibility threshold. If relevant residue limits cannot be satisfactorily determined by a validated analytical method, dedicated facilities are required.

In summary, while the ADE (PDE) is the number that sets your ultimate acceptable contamination threshold, it is the full HBEL report and its documented rationale that provide the necessary scientific foundation to justify that the risk is adequately controlled and that you are meeting the expectations of EMA and PIC/S for pharmaceutical manufacturing in shared facilities. If you only have the number, you lack the scientific proof, the necessary rationale for inspectors, and the critical context needed to implement a defensible control strategy.