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📅 Last Updated: October 29, 2026
SCDM (soybean casein digest medium) and TSB (tryptic soy broth) are the same type of general-purpose, non-selective liquid medium. SCDM is the pharmacopoeial name and TSB is the common trade name. A media fill, also called aseptic process simulation (APS), fills this medium in place of product. A clean run means something only if the medium can grow organisms. Growth promotion testing (GPT) proves that.
What Are SCDM and TSB in Media Fill?
SCDM and TSB are the two names you meet most often for the liquid poured into vials, bottles and bags during a media fill. Tryptic soy broth, sold in some regions as tryptone soya broth (TSB), is the name on most supplier labels. For the full overview of the run itself, see What is Media fill in Pharmaceutical.
Both are built on casein and soy peptones, and both are general-purpose and non-selective, so they do not favour one group of organisms over another.
Supplier formulations differ slightly, so the label name alone does not settle anything. The QC analyst compares the formula and the certificate of analysis of the lot received with the medium named in the validated procedure.
FDA’s 2004 aseptic processing guidance, section VII, says a microbiological growth medium such as soybean casein digest medium should generally be used. It adds that anaerobic media, for example fluid thioglycollate medium, should be considered only in special circumstances.
Why Does the SCDM TSB Growth Promotion Test in Media Fill Matter?
The medium is the detector. Think of a smoke alarm: if nobody has ever tested it, silence tells you nothing. A media fill works the same way, because the target result is no growth. Annex 1 (2022), paragraph 9.46, states that the target should be zero growth and that any contaminated unit fails the APS.
Annex 1 paragraph 9.32 describes APS as a periodic verification of the effectiveness of aseptic controls, using sterile nutrient media or a surrogate in place of product. It is not the primary means of validating the aseptic process. Process design, the quality system, training and monitoring data carry that weight.
The same paragraph says the medium or surrogate should be chosen for its ability to imitate the physical product characteristics that pose a sterility risk. Where a surrogate such as a buffer is used in part of the run, it must not inhibit the growth of any contamination.
For sterile active substances, paragraph 9.37 asks for all simulation materials, growth medium and surrogates alike, to be microbially evaluated so they do not compromise recovery. Paragraph 9.42 adds that discarded material such as a product flush is simulated with nutrient media and incubated.
What Is Growth Promotion Testing and When Is It Done?
Growth promotion testing (GPT) is a laboratory test that shows a batch of medium supports the growth of a defined set of organisms. The organisms are added at a low count. It answers one question: will this medium turn cloudy if a contaminant is present?
Annex 1 paragraph 9.36 vi says the selected nutrient media should be capable of growing a designated group of reference microorganisms described by the relevant pharmacopoeia. It adds suitably representative local isolates. FDA 2004, section VII, asks for demonstrated growth of gram-positive and gram-negative bacteria, yeast and mould, for example USP indicator organisms. The challenge is fewer than 100 CFU (colony-forming units, the count of viable organisms).
FDA also says the QC laboratory should decide whether the USP organisms represent production-related isolates. Isolates from environmental monitoring and sterility tests can be added or substituted where appropriate.
Many sites test every new lot on receipt, as in this procedure for growth promotion test in microbiology. Ready-made media usually arrive with supplier GPT evidence, and the site decides what incoming checks to add. The timing belongs in the site SOP and the pharmacopoeial or validated procedure.
GPT of the medium versus positive control of filled units
These are two different steps. GPT is done in the laboratory on the medium. The positive control in Annex 1 paragraph 9.45 ii is done after incubation. Samples of the filled APS units are inoculated with a suitable range of reference organisms and representative local isolates. It shows that the medium, after sitting in the real containers and passing through the process, still grows organisms.
What Do the Standards Say About Organisms, Incubation and Acceptance?
Annex 1 and the FDA guidance do not say the same things, and neither is a pharmacopoeia. The table keeps them apart.
| Item | EU GMP Annex 1 (2022) | FDA guidance (2004) |
|---|---|---|
| Medium growth ability | 9.36 vi: reference organisms per pharmacopoeia plus local isolates | Section VII: gram-positive, gram-negative, yeast, mould; inoculum below 100 CFU |
| Incubation | 9.44: conditions and duration scientifically justified and validated; no day count | Not less than 14 days; 20–35 °C, held within ±2.5 °C of target |
| Two temperatures | Not specified | At least 7 days at each, lower temperature first |
| Acceptance | 9.46: target is zero growth; any contaminated unit fails | Recommended criteria by run size (below) |
| Run size | 9.40: typically 5,000 to 10,000 units; small batches at least equal to production batch | Starting point 5,000 to 10,000 units; small operations at least the maximum batch size |
FDA’s criteria are recommendations, not limits. Under 5,000 units, no contaminated unit should be found, and one contaminated unit is cause for revalidation after investigation. For 5,000 to 10,000 units, one contaminated unit triggers an investigation that considers a repeat media fill, and two are cause for revalidation. Above 10,000 units, one triggers an investigation and two are cause for revalidation. Annex 1 is stricter in wording: a single contaminated unit fails the APS.
The strains, exact inoculum, incubation conditions and acceptance criterion for the laboratory GPT come from the pharmacopoeial chapter or validated procedure your site follows. They differ between chapters, so this article does not restate them as one universal set.
PIC/S publishes its own version of the Annex 1 guide under PE 009, used by inspectorates in PIC/S member countries.
How Do You Prepare, Store and Handle the Medium?
Treat the medium like any other critical material: defined, prepared by a validated method and traceable to a lot.
- Select the medium in the APS protocol and justify it against the product and the process.
- Prepare it as the supplier instructs, unless a different method is scientifically justified and documented.
- Sterilise it by a validated method. Heat, filtration and gamma irradiation are all in use, and ready-made irradiated bags or dry powder are common options.
- Run GPT on the lot, or file the supplier’s GPT evidence together with your incoming checks, as the SOP requires.
- Label it with lot, preparation date, expiry and storage conditions.
- Fill a volume that wets every surface and leaves headspace.
- Swirl or invert the sealed units before incubation.
There is no universal shelf life or hold time for prepared medium. Ready-made medium follows the supplier’s label and certificate of analysis. Medium prepared in house needs an in-use shelf life and hold times set from the site’s own data. Your internal SOP for storage and preparation of media and culture is the place to record them.
How Does Medium Suitability Affect Contamination Detection?
A medium that passes GPT can still hide contamination if the rest of the set-up is weak. Annex 1 spreads the detection requirement across several paragraphs.
Paragraph 9.36 iv asks for a fill volume large enough for the medium to contact all equipment and component surfaces. It also asks for enough headspace to support growth and let turbidity show. Paragraph 9.41 requires agitating, swirling or inverting units before incubation, so that the medium contacts every interior surface. All integral units are incubated, including those with cosmetic defects.
Paragraph 9.43 calls for clear containers, or a validated detection method where the product container is amber or opaque. Isolates from contaminated units are identified to species level when practical. Paragraph 9.45 i says trained and qualified personnel inspect the units under conditions that make contamination easy to see.
FDA adds that a damaged unit found after incubation has started stays in the run data, and excluding it needs full justification in the report.
Why Is 3% SCDM Used in Media Fill?
The 3% most likely refers to the powder strength of the medium, expressed as weight per volume (w/v). Where sites quote 3% SCDM, it usually means about 30 g of dehydrated medium in 1 litre of water, which matches many supplier label directions.
It is a usual practice, not a regulatory requirement. Neither Annex 1 (2022) nor the FDA 2004 guidance names a medium concentration. Paragraph 9.36 vi only requires that the medium grow the reference organisms and local isolates. Some web pages call 3% a global standard, but none of them points to an official text that says so.
So the honest answer is practical. Sites choose a strength, usually the supplier’s standard, because it is familiar and well characterised. They then justify it in the protocol and show by GPT that it supports growth. If a site used a different strength, the same logic would apply.
How Is GPT Different from Environmental Monitoring, Sterility Testing and the Run Assessment?
| Activity | Question it answers | Sample |
|---|---|---|
| Growth promotion test | Can this medium grow organisms? | Medium, inoculated in the laboratory |
| Environmental monitoring | Is the cleanroom within its limits? | Air, surfaces, personnel |
| Sterility test | Does this product sample pass? | Product sample |
| Media fill run assessment | Did the aseptic process stay free of contamination? | Incubated filled units, plus records |
Annex 1 paragraph 9.36 xi expects routine environmental monitoring throughout the APS, so its data are reviewed with the result. The run is judged on contaminated units, the interventions performed, personnel, monitoring data and any investigation. A good GPT result does not make a run pass, and a clean sterility test does not replace a media fill.
Recent Technology Trends
Annex 1 (Commission document C(2022) 5938 final) was published on 25 August 2022. Its text sets 25 August 2023 as the deadline for coming into operation, with 25 August 2024 for point 8.123 only. Many sites rewrote APS protocols and medium controls around that date.
The PDA lists Technical Report 22 on process simulation as revised in 2025. Only the bookstore listing was available, so the details of its medium guidance are not covered here.
A supplier white paper from WILCO describes automated inspection of media-filled vials by laser headspace analysis of CO2 and O2. It is offered as an objective alternative to visual turbidity checks. The paper is undated and the claim is the vendor’s. Under Annex 1 paragraph 9.36 vii, any detection method must be scientifically justified so that contamination is reliably detected.
Common Mistakes and Troubleshooting
GPT fails on a lot of medium
Possible causes:
Wrong or over-passaged culture, an inoculum above the allowed count, overheated medium, or a damaged lot.
Corrective actions:
Open a deviation and investigate the cause of the failure. FDA 2004 says that if growth promotion fails, the origin of any contamination in the run should still be investigated and the media fill promptly repeated.
Turbid units after a passed GPT
Possible causes:
Real contamination of the process, not a medium problem. The passed GPT shows the medium could grow organisms, which makes the turbidity more credible.
Corrective actions:
Identify the isolate to species and compare it with the environmental monitoring flora. Then follow Annex 1 paragraph 9.46: investigation, corrective measures, repeat APS and a review of batches made since the last successful APS.
No growth, but doubts about the medium
Possible causes:
Too little fill volume, units not swirled or inverted, medium held beyond its validated time, or inspection by untrained staff.
Corrective actions:
Review fill volumes, hold times and inspector qualification before accepting the result.
Units excluded without a reason
Damaged or defective units dropped from the tally without written justification. Annex 1 paragraph 9.47 asks for a full reconciliation of units filled, incubated and not incubated.
Documentation and QA Review Points
The QA officer reviewing an APS package should find the following in the record:
- The medium used, supplier, lot, certificate of analysis, preparation record and sterilisation record
- The GPT report with strains, passage level and results, or the supplier’s evidence and the incoming check
- The positive-control record for the filled units, using reference organisms and local isolates
- Unit reconciliation, intervention log with start and end times, and environmental monitoring data
- Incubator temperature logs, inspector qualification records and the identification of any isolate
Incubator logs and inspection sheets should follow the principles of ALCOA and ALCOA+ data integrity. A failed APS goes through deviation, investigation and CAPA, and changes to the medium or its supplier go through change control.
- Describe the medium fully in the protocol. Write supplier, product code, strength and sterilisation method, not just “TSB”.
- Test the lot you fill with. A GPT on a previous lot does not cover the one in the vessel.
- Keep strain records tight. Record source, passage level and expiry of every culture used for GPT and positive control.
- Include local isolates. Pull them from environmental monitoring and sterility test history, as Annex 1 expects.
- Fill for visibility. Leave headspace so turbidity can be seen, and swirl every unit.
- Qualify inspectors. Run periodic test sets of known turbid and clear units.
- Write the 3% rationale down. A single justified line in the protocol saves a long audit discussion.
- Treat a GPT failure as a deviation. Never repeat the test quietly until it passes.
Frequently Asked Questions
They are the same type of medium sold under two titles. SCDM is the pharmacopoeial term and TSB is the common trade term, and both are general-purpose, non-selective liquids made from casein and soy peptones. Supplier formulations differ slightly, so QC compares the formula and certificate of analysis of the product bought with the medium called for in the validated procedure.
No. Annex 1 (2022) and the FDA 2004 guidance set no medium concentration. The figure is usually 3% w/v, about 30 g of powder per litre, and reflects common supplier directions and industry habit. Whatever strength your site uses must be justified in the protocol and shown to support growth through growth promotion testing.
Sites usually test each new lot of medium on receipt, and ready-made media are covered by supplier evidence plus the site’s incoming checks. The exact timing is set by the pharmacopoeial chapter or validated procedure and the site SOP. Annex 1 separately requires positive control of the incubated filled units after incubation.
Annex 1 (2022) paragraph 9.44 asks for incubation conditions and duration that are scientifically justified and validated, and gives no day count. FDA’s 2004 guidance recommends at least 14 days between 20 and 35 °C. If two temperatures are used, it recommends at least 7 days at each, starting with the lower.
Annex 1 paragraph 9.36 vi says the medium should grow pharmacopoeial reference organisms and suitably representative local isolates. Paragraph 9.45 ii applies the same idea to positive control of filled units. FDA says the QC laboratory should decide whether USP organisms represent production isolates, and may add or substitute isolates from environmental monitoring and sterility tests.
Treat it as a deviation. FDA 2004 says that if growth promotion fails, any contamination in the run must still be investigated and the media fill promptly repeated. The cause of the GPT failure should also be investigated. A run on a medium that failed GPT cannot support a zero-growth conclusion.
No. GPT shows that the medium can grow organisms. Environmental monitoring samples the cleanroom, and sterility testing examines a product sample. The media fill run is judged on contaminated units, interventions, monitoring data and any investigation. Each answers a different question, and none can stand in for another.
Summary
SCDM and TSB are the same type of non-selective medium, and the medium is only a reliable detector once GPT and positive control prove it. Annex 1 sets a zero-growth target and requires justified, validated incubation. FDA 2004 gives 14 days. The 3% strength is common practice, not a rule.
References
- Annex 1: Manufacture of Sterile Medicinal Products (C(2022) 5938 final), European Commission
- Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing, Current Good Manufacturing Practice (October 2004), US FDA
- Sterile Drug Products Produced by Aseptic Processing, guidance page, US FDA
- PIC/S Publications (PE 009 Guide to GMP), PIC/S
- PDA Technical Report No. 22 (Revised 2025): Process Simulation for Aseptically Filled Products, PDA
- Aseptic Process Simulation (APS), Merck/Sigma-Aldrich
- Why 3% Soybean Casein Digest Medium (SCDM) is Used for Media Fill Validation, pharmaceuticalmicrobiology.in
- Automated media fill inspection, WILCO AG
- USP and Ph. Eur. general chapters on microbial examination and sterility testing, current editions
Satpal Singh — Quality Assurance & Regulatory Specialist
Satpal Singh is an experienced pharmaceutical Quality Assurance and Regulatory professional with expertise in GMP compliance, quality systems, technical documentation, and regulatory requirements. He reviews our pharmaceutical content to ensure accuracy, industry relevance, and alignment with current quality and regulatory standards.
Expertise: QA Systems | GMP Compliance | Regulatory Documentation | Audits | Quality Management