Pre-Procedure Antiseptic Efficacy Studies at CREM Co Labs

Introduction

Pre-procedure antiseptic skin preparation products – including preoperative, precatheterization, and preinjection skin preparations – are critical in preventing infections during medical procedures. CREM Co Labs plays a pivotal role in evaluating the efficacy of these antiseptic drug products under rigorous, regulatory-grade conditions. We offer end-to-end efficacy evaluation studies (in vitro and in vivo) to demonstrate how well a skin prep reduces microbial flora on the skin before surgery, catheter insertion, or injection. Our studies are designed to meet FDA and Health Canada requirements, using precise scientific methods and language suitable for regulatory submissions. By leveraging GLP-compliant laboratory testing and GCP-compliant clinical simulations, CREM Co Labs provides data that support your product’s safety and efficacy for regulatory approval.

Regulatory Framework

CREM Co Labs designs each study in strict alignment with both U.S. FDA and Health Canada efficacy requirements for antiseptic skin preparations. We adhere to the standardized test methods and guidelines that these agencies recognize, ensuring our results are accepted on both sides of the border:

ASTM E1173 Compliance: All in-vivo efficacy studies follow ASTM E1173, the standard test method for evaluating preoperative, precatheterization, or preinjection skin preparations. This ensures a consistent approach to measuring microbial reduction and persistence on skin, as expected by regulators.
FDA Final Rule (Health Care Antiseptics): Our protocols incorporate FDA’s latest rules (82 FR 60474, 2017 and subsequent updates) on health care antiseptics. FDA emphasizes that patient preoperative skin preps must demonstrate both immediate antimicrobial effect and persistent activity, whereas patient preinjection skin preps (for quick injections) do not require persistent activity due to the brief nature of injections. We design studies accordingly – e.g. testing preinjection products for rapid kill at 30 seconds post-application without a long-term persistence requirement. For preoperative and precatheterization products, we include prolonged post-application sampling to prove persistence, since FDA expects a 6-hour post-treatment bacterial count that is no higher than the baseline count in 100% of subjects.
Health Canada Guidance: Our studies equally satisfy Health Canada’s Guidance Document: Human-Use Antiseptic Drugs. Health Canada requires that all surgical and preoperative skin preparations demonstrate at least 6 hours of persistent antimicrobial activity. We ensure our in-vivo study designs include this persistence evaluation against both bacteria and fungi, per Canadian guidelines. Moreover, we meet Health Canada’s efficacy benchmarks, such as achieving a ≥3 log₁₀ reduction on high-bacterial-load (moist) skin sites and ≥2 log₁₀ on dry skin sites during testing. These log reduction criteria for moist and dry sites are harmonized with FDA’s expectations and underscore the need to show robust initial efficacy on different skin types.
Harmonized Approach: By conforming to both FDA and Health Canada standards, we provide a dual-compliant data package. Whether your product submission is to the FDA, Health Canada, or both, our efficacy evaluation studies cover the necessary regulatory endpoints – including time points like 30 seconds, 10 minutes, and 6 hours post-application as mandated. This comprehensive approach eliminates duplicate testing and streamlines your regulatory strategy.

Efficacy Evaluation Studies

We employ a two-pronged strategy to thoroughly evaluate antiseptic efficacy: GLP-compliant in vitro testing and GCP-compliant in vivo studies. This integrated approach ensures that your pre-procedure skin prep is vetted both in the controlled lab and in real-world simulated use on human skin:

GLP In Vitro Testing: Before testing on humans, we conduct rigorous laboratory assays under Good Laboratory Practice. These in vitro tests (such as time-kill studies and minimum inhibitory concentration determinations) establish the formulation’s antimicrobial spectrum and potency. We challenge the product against a panel of bacteria (and fungi, as required) commonly implicated in surgical site or catheter-related infections, following standardized methods. All in vitro work is executed with full GLP documentation, ensuring traceability and quality of data. By confirming the product’s activity in vitro, we set a strong foundation for subsequent clinical simulations and ensure the test method (including neutralizers and media) is effective before proceeding in vivo.
GCP In Vivo Studies: The core of our efficacy program is the in vivo study, conducted on healthy volunteer subjects under Good Clinical Practice conditions. These studies are essentially clinical simulations of how the product is used in practice. We apply the antiseptic product to defined test sites on the skin (e.g. abdomen, inguinal crease, forearm) and measure the reduction of the skin’s resident microflora at specific intervals after application. Typical regulatory-driven sampling intervals include:
- Baseline (pre-application): To quantify the starting bacterial load.
- Immediate post-application (e.g. 30 seconds after product dries for preinjection uses, or 10 minutes for preoperative uses as an alternative initial timepoint) to assess rapid kill.
- Extended post-application (e.g. 6 hours post-application) to assess residual (persistent) antimicrobial activity. Longer intervals (12 or 24 hours) can also be evaluated for precatheterization antiseptics, per ASTM E1173 guidance, if needed.
At each interval, microbial samples are taken from the skin and analyzed to determine how many organisms remain. Our dual approach – combining GLP lab data with GCP clinical results – provides robust evidence of efficacy. The in vitro results guide and corroborate the in vivo findings, while the in vivo study ultimately demonstrates regulatory-grade efficacy in humans using the appropriate methodology.

Throughout these efficacy evaluation studies, we avoid the term “confirmatory testing.” Instead, we focus on prospective, regulatory-aligned efficacy evaluations that generate the required evidence for product approval. CREM Co Labs manages the entire process, from protocol development through execution and analysis, ensuring that each study is scientifically sound and compliant.

Methodology: Study Design & Microbial Sampling

Our methodology follows industry best practices and official standards to accurately measure antiseptic performance:

Test Site Selection: We test products on both moist skin sites (like the inguinal crease or axilla) and dry skin sites (such as the forearm or abdomen) to represent different skin flora conditions. This is important because moist areas typically harbor higher bacterial counts than dry areas. Per ASTM E1173, we ensure baseline bacterial populations are sufficiently high – at least 3 log₁₀ above detection limit on moist sites and ≥2 log₁₀ above detection on dry sites– to meaningfully measure log reductions. High baseline counts create a worst-case challenge for the antiseptic and reduce variability in the data.
Cup Scrub Sampling Technique: We employ the standardized “cup scrub” method (also known as the cylinder scrub technique) to sample skin microorganisms. In this technique, a sterile cylinder (cup) is securely placed on the skin at the test site and filled with a known volume of sterile sampling fluid containing appropriate neutralizers. A technician uses a sterile rubber policeman (scrubbing rod) to gently rub the skin within the cup for about one minute, dislodging bacteria from the skin into the fluid. The fluid – now containing the skin flora – is then recovered, serially diluted, and plated on growth media. This allows us to count the colony-forming units (CFUs) and determine the bacterial load at each sampling point. The cup scrub method is widely regarded as the gold-standard for in vivo skin antiseptic testing, as it recovers more bacteria than swabbing or other non-destructive methods while leaving the skin intact for repeated sampling.
Controls and Study Arms: Each study is carefully controlled for scientific validity. FDA’s guidance recommends a three-arm study design for antiseptic efficacy trials – including the test product, a known effective active control, and a negative control (e.g. the product’s vehicle or saline). CREM Co Labs can incorporate this design to satisfy regulatory expectations. For example, one group of subjects (or skin sites) receives the test antiseptic, while another group might receive a reference standard prep (active control) and a third receives a placebo or no active ingredient. This setup allows us to demonstrate that the test product is significantly more effective than no treatment, and not inferior to an established product. We randomize treatment assignments (e.g. which site gets which product and at which time) to avoid bias. All personnel performing bacterial counts are blinded to the treatment to ensure objective measurements.
Application and Exposure: Trained technicians apply the skin prep products according to their instructions for use (e.g. applying with friction for a specified duration, then allowing to dry completely). We time the application carefully and start the clock for sampling intervals once the site is dried, as per the product’s usage directions. If the protocol requires the site to remain undisturbed for a persistence interval (e.g. 6 hours), we cover it with a sterile dressing or drape to prevent external contamination while avoiding occlusion that could affect the product’s action. Volunteers are instructed not to touch or wash the area during this period.
Microbial Recovery & Neutralization: Our laboratory team processes the collected samples immediately to maintain viability of organisms. The sampling fluid contains neutralizers specific to the antiseptic’s active ingredients (such as polysorbates or lecithin) to instantly quench any residual antiseptic in the sample. This step is crucial – it ensures that any continued kill happens only on the skin, not in the sample cup, so that our CFU counts accurately reflect the moment of sampling. Each sample is diluted as needed and plated in duplicate on appropriate agar to culture aerobic bacteria (and fungi, if required). We incubate the plates and then count colonies to determine the log₁₀ CFU/cm² present at baseline and after treatment.
Statistical Endpoints: We analyze the data to calculate the log₁₀ reduction from baseline for each time point and each subject, as well as group averages and confidence intervals. Our statisticians then apply the required statistical tests per regulatory guidelines. For instance, we can use the FDA-recommended linear regression model (Average Treatment Effect approach) to compare the test product to controls. We will demonstrate that the test product achieves:
- Superiority to the negative control: e.g. at least a 1.5 log₁₀ greater reduction than the vehicle, ensuring the effect isn’t just from the act of scrubbing.
- Non-inferiority to the active control: e.g. within 0.5 log₁₀ of the reference product’s performance (or better, if required to show effectiveness).
- Regulatory Thresholds Met: We confirm that the product meets or exceeds the threshold log reductions (e.g. ≥3 log₁₀ on moist sites) stipulated by FDA/Health Canada. We also verify persistence by analyzing the 6-hour samples: for a surgical prep, virtually all subjects should show at least as low a bacterial count at 6 hours as they did at baseline, indicating no regrowth.
Data Integrity: Every step from sample collection to CFU counting is documented under our Quality Assurance oversight. We include appropriate controls on the microbiological methods too – for example, performing recovery efficiency checks and using positive control bacteria to validate neutralization effectiveness (ensuring the neutralizers inactivate the antiseptic without harming the microbes’ viability).

By following this meticulous methodology, we obtain credible and reproducible results. The use of a standardized cup scrub technique and a robust control design gives regulators confidence that the efficacy outcomes are due to the product’s true performance. Our attention to statistical rigor and method validation means the study outcomes are not just pass/fail, but provide insight into the product’s kill kinetics and persistence profile.

Ethics & Volunteer Safety

Conducting in vivo antimicrobial studies on human volunteers requires the highest ethical standards. At CREM Co Labs, volunteer safety and rights are paramount, and our clinical testing is carried out with full GCP (Good Clinical Practice) compliance:

Ethics Oversight: Before any study begins, the protocol is reviewed and approved by an independent Institutional Review Board (IRB) or Ethics Committee. This review ensures that the study’s design is ethical, the risk to participants is minimized, and informed consent materials are clear.
Informed Consent: We obtain written informed consent from all volunteer participants after explaining the study procedures, any potential risks (such as transient skin irritation), and their rights (including the right to withdraw at any time). Participants are typically healthy adults screened for eligibility – for example, we exclude individuals with dermatological conditions, known allergies to antiseptic ingredients, or other factors that might increase risk.
Trained Medical Supervision: Our in vivo studies are overseen by medical professionals (investigators) experienced in dermatological research. During the study, volunteers are closely monitored. We check for any signs of adverse reactions on the treated skin, such as redness, itching, or allergic response, at each sampling interval and afterwards. A physician is on-call during the study to address any medical concerns, however minor.
Minimized Risk Procedures: The sampling method (cup scrub) is designed to be gentle and nondestructive, meaning it should not damage the skin. It is roughly equivalent to a vigorous washing; volunteers typically experience no more than mild temporary skin redness from friction. We also use sterile equipment and aseptic technique to prevent any chance of infection or contamination of the volunteer’s skin during sampling. After study completion, an appropriate moisturizer or after-care is provided if needed to ensure the skin fully recovers.
GCP Documentation: We maintain complete GCP records, including the study protocol, IRB approvals, consent forms, case report forms for each volunteer, and records of any deviation or adverse event. Our team conducts the study according to the protocol and GCP guidelines so that the data are reliable and ethically obtained. This includes adhering to randomization codes, blinding where possible, and secure data handling. Volunteers’ confidentiality is protected; any samples or data are coded and cannot be traced to personal identities.
Volunteer Compensation and Follow-Up: Typically, volunteers receive a reasonable compensation for their time and inconvenience. We also provide a safety follow-up, checking in with participants after the study to ensure no delayed effects (for example, confirming a few days later that there’s no lingering skin reaction). This comprehensive care helps build trust and ensures volunteer welfare.

By upholding these ethical and safety measures, CREM Co Labs not only protects participants but also ensures that the study outcomes are respected by regulatory authorities. Data from a GCP-compliant study carries weight because it guarantees that the trial was conducted with the same rigor as a clinical trial for a new drug. Our commitment to ethics and volunteer safety ultimately enhances the credibility of the efficacy data we generate for your antiseptic product.

Deliverables

Upon completion of the efficacy evaluation studies, CREM Co Labs provides a comprehensive documentation package ready for inclusion in your regulatory submissions. Our deliverables include:

Complete Study Reports: A detailed final report for each study (in vitro and in vivo), prepared in a format suitable for FDA and Health Canada dossiers. The reports describe the study rationale, methodology, protocol deviations (if any), and results. They include clear narratives and tables/graphs of the log reduction results at each time point for the test product and controls.
GLP and GCP Compliance Statements: Each report contains statements of GLP compliance (for lab studies) and GCP compliance (for clinical studies), signed by our Quality Assurance Unit. We also provide copies of QA audit certificates and IRB approvals in the appendices, demonstrating that the studies met all quality and ethical standards.
Statistical Analysis & Interpretation: We include the full statistical analysis output, including calculations of log reductions, confidence intervals, and statistical comparisons (e.g. non-inferiority and superiority tests). The report explains whether the product met the pre-specified acceptance criteria and what the margins of efficacy were. We interpret the data in context, for example: “Product X achieved a mean 3.5 log₁₀ reduction at 30 seconds on inguinal sites, exceeding the FDA/HC requirement of 3 log₁₀.” This gives the reader (and regulators) a clear understanding of efficacy.
Appendices (Raw Data and Supporting Documents): We provide all relevant raw data in structured appendices. This includes individual subject data sheets (with baseline and post-treatment CFU counts per sample), plate count records, and any calibration records for equipment used. We also attach the study protocol, volunteer informed consent template, and any additional documentation required by regulators (e.g. training records of personnel, if requested). For GLP studies, we include raw laboratory worksheets; for the clinical part, we include case report forms and microbiology result printouts. These appendices ensure transparency – an inspector or reviewer can trace any summarized result back to its source.
Regulatory Summary and Dossier-Ready Format: We understand that our clients will use these results in submissions like FDA New Drug Applications (NDAs), Health Canada New Drug Submissions (NDS), or DIN applications for antiseptics. Therefore, we can provide summary documents formatted for the Common Technical Document (CTD) sections (e.g. a synopsis for Module 2 and the full report for Module 5 in an NDA). We ensure that tables, figures, and section headings meet the expected format, which can save you significant time in preparing your dossier. We also cross-reference relevant guideline documents in the report so that reviewers see alignment with requirements (for instance, citing ASTM E1173 or the Health Canada guidance within the discussion of results).
Certificate of Analysis for Test Materials: If needed, we include documentation on the test product’s identity and concentration. For example, confirmation of the active ingredient content in the batch used for testing (to show it was within specification) can be provided, as this may be required to tie the efficacy results to a particular lot of product.
Consultation for Regulatory Queries: Our involvement doesn’t end with delivering the report. We remain available to help address any questions from regulatory agencies regarding the study. Because we meticulously document and follow guidelines, our reports often preempt questions, but if an agency requires clarification, we provide the scientific and technical support to our clients. This can include additional analyses, justifications, or even testimony by our experts.

All deliverables are provided in electronic format (and hardcopy upon request), with a professional, peer-reviewed presentation. The thoroughness of these deliverables means you can directly insert them into your regulatory submissions with confidence. CREM Co Labs’ output effectively becomes a ready-to-file component of your product’s regulatory package, reducing your preparation workload and expediting the review process.

Why CREM Co Labs?

Choosing CREM Co Labs for your antiseptic drug efficacy studies offers several distinct advantages:

Proven Regulatory Compliance: We operate under strict GLP and GCP standards, which is essential for regulatory-grade studies. Our laboratory and clinical processes have successfully passed audits, and data generated are readily accepted by regulatory authorities. By following official methods (like ASTM E1173) and guidelines to the letter, we ensure there are no surprises during agency reviews.
Expertise in Antiseptic Efficacy: Our team has extensive experience specifically with preoperative, precatheterization, and preinjection skin prep products. We stay up-to-date with evolving regulations – from FDA’s final rulemaking on health care antiseptics to Health Canada’s guidance revisions – and we incorporate the latest requirements (for example, statistical analysis techniques or new sampling standards) into our study designs. This expertise allows us to advise you on the optimal study parameters and to troubleshoot any technical challenges (such as selecting appropriate neutralizers for novel active ingredients).
Integrated In Vitro & In Vivo Capabilities: Unlike many contract labs, CREM Co Labs offers a one-stop solution for both laboratory microbiological testing and clinical in vivo trials. Our microbiology lab and clinical trial unit work in tandem, ensuring seamless progression from bench to human testing. This integrated approach not only saves time but also ensures consistency – the same scientific leadership oversees all phases, maintaining continuity in methodology and data interpretation.
Quality and Integrity of Data: We recognize that antiseptic efficacy studies will be scrutinized in detail by regulatory reviewers. Therefore, we build quality checks into every step of the process. Our data integrity practices (electronic data capture, audit trails, sample tracking, etc.) ensure that the results are reliable and defendable. We also run pilot tests and method validations upfront to de-risk the pivotal studies. By the time we conduct the official efficacy study, all methods have been refined for accuracy and reproducibility.
Tailored, Submission-Ready Outputs: CREM Co Labs takes pride in delivering results in a clear, organized manner. The reports we provide not only document results but also explain their significance in regulatory terms, which is invaluable for your internal teams and the regulators reviewing your dossier. We understand the language of regulators and ensure our documentation uses precise scientific and regulatory terminology. The high-quality summaries, graphs, and statistical analyses in our reports often can be directly repurposed in your product’s labeling or marketing applications, saving you effort.
Collaborative Approach: From the moment you engage with us, we act as a collaborative partner. We can assist in protocol development and even interact with regulators on your behalf (for example, to discuss a study plan in a pre-submission meeting). Our scientists are accessible to answer your questions throughout the project. We also maintain flexibility – if you need to adjust the study (say, add an extra time point or run an additional organism test), we accommodate such changes while keeping the project on track. We strive to function as an extension of your R&D team, dedicated to the success of your product.
Track Record of Success: CREM Co Labs has successfully executed numerous antiseptic efficacy studies that have supported product approvals in the US and Canada. Our case studies include skin prep solutions for major pharmaceutical and medical device companies (all client information kept confidential). This experience translates into efficient project management and knowledge of potential pitfalls. When you choose us, you benefit from our cumulative experience with similar products and studies.

In summary, CREM Co Labs offers a comprehensive, competent, and compliant solution for evaluating the efficacy of preoperative, precatheterization, and preinjection skin antiseptic drugs. We help you navigate the complex regulatory expectations with confidence. By demonstrating your product’s efficacy through our studies – meeting all FDA and Health Canada criteria – you can bolster your regulatory submissions and ultimately bring a safe, effective antiseptic solution to the market to improve patient care.