Standards for Biological Raw Materials in Japan

Document overview and legal status

Japan’s Standards for Biological Raw Materials are a Ministry of Health, Labour and Welfare (MHLW) notification-based standard. The PMDA English version is a provisional translation (as of May 2024), and the document lists an initial enactment on May 20, 2003 (MHLW Notification No. 210) with multiple partial revisions, most recently February 28, 2018 (MHLW Notification No. 37). Reference: PMDA PDF.

Purpose: what the standards are trying to control

These standards specify criteria for measures needed when drugs, quasi-drugs, cosmetics, medical devices, and regenerative medical products are manufactured using raw materials (including additives and media used in manufacturing) derived from humans or other organisms (excluding plants), to ensure quality, efficacy, and safety.

Scope and key exclusions

The standards do not apply to:

• raw materials used to manufacture in vitro diagnostics and other products not directly used in the human body, and
• microorganisms and viruses used to manufacture vaccines, etc.

How the standards are structured

The table of contents organizes requirements into four major parts:

1. General Notices (definitions and overarching rules)
2. General Rules for Blood Products (for transfusion; and plasma derivatives)
3. General Rules for Human-Derived Raw Materials (human cell/tissue-based, human-urine-derived, and other human-derived)
4. General Rules for Animal-Derived Raw Materials (ruminant-derived; animal cell/tissue-based; and other animal-derived)

Cross-cutting concepts you must document and control

“Raw materials, etc.” includes more than the ingredient itself

The document defines “source material” and clarifies that “raw materials, etc.” includes raw materials, ancillary materials, and their source materials, reflecting a supply-chain/traceability mindset beyond the direct active ingredient.

Donor screening, window period, and traceability are core

The standards define donor, donor animal, donor screening, and window period, signaling that eligibility determination and infectious-risk timing are central to compliance planning.

Risk-based flexibility exists (but must be justified)

The standards state that certain provisions are not applied where an approval letter confirms equivalent or superior validity for quality and safety, and that approved products used as raw materials may be regarded as conforming (when appropriately used).

Selected requirements by material type

1) Blood products for transfusion: donor eligibility, testing, storage, records

For blood products for transfusion, the standards require that blood donors be considered eligible and free from bloodborne infectious disease via interview, etc., unless inactivation/removal is confirmed and described in the approval letter. They require, at minimum, serological testing for Treponema pallidum, HBV, HCV, HIV-1/2, and HTLV-1, and nucleic acid amplification tests for HBV DNA, HCV RNA, and HIV RNA, with clear “do not use” rules when results indicate ineligibility or viral presence. They also specify preservation temperature (generally 1–10°C) and require comprehensive recording and storage of collection site/date, donor medical examination records, serology/NAT results, working records, donor identifiers, and other safety-relevant information.

2) Plasma derivatives: controls extend to source plasma

For plasma derivatives, the standards similarly require donor eligibility determinations and infectious-risk controls (with a comparable inactivation/removal exception when documented in the approval letter). They require serology (at least HBV, HCV, HIV) and NAT on source plasma (at least HBV DNA, HCV RNA, HIV RNA), plus defined storage conditions (including ≤6°C for preserved source plasma) and detailed traceability/record-keeping across blood, processing into source plasma, and unique manufacturing identifiers.

3) Human cell/tissue-based raw materials: controlled collection and contamination prevention

Human cell/tissue-based materials must be collected in facilities with adequate personnel/equipment for sanitation management, with measures to prevent contamination by microbial and other pathogenic agents.

4) Animal-derived materials: viral-risk verification and special attention to ruminants (TSE)

For animal cell/tissue-based raw materials, the standards require sanitary collection, contamination prevention measures, donor-animal eligibility, and confirmation of viral infection risk verification and other required tests. For ruminant-derived materials, the standards emphasize safety-critical information recording (e.g., origin country, preparation date, breeding/slaughter conditions, and measures related to prevention of transmissible spongiform encephalopathy spread, plus lot numbers), reflecting prion/TSE risk management expectations.

Practical compliance checklist (early planning)

• Map all raw materials, ancillary materials, and source materials and decide which sections apply.
• Build a traceability and record retention system that can link lots to donor/animal eligibility and testing results.
• For blood/plasma inputs, ensure minimum serology + NAT panels and storage conditions are operationally feasible and auditable.
• For human cell/tissue inputs, validate collection-site controls and contamination-prevention procedures.
• For ruminant/animal inputs, confirm TSE/viral-risk documentation and supplier record availability before locking the supply chain.

Reference: PMDA PDF.