PharmaCalc

Maximum Allowable Carryover (MACO) for cleaning validation. Formulas, variables, and step-by-step method for the Therapeutic Dose, 10 ppm, HBEL/ADE, and LD50/NOEL approaches with GMP PDF reports.

Health-Based Exposure Limit / Permitted Daily Exposure per EMA/CHMP/SWP/169430/2012. Derives PDE from NOAEL or LOAEL toxicology data with F1–F5 adjustment factors — formulas, variables, and worked method.

Swab recovery study statistics: mean recovery, sample SD, %RSD, and 95% CI via t-distribution, evaluated against ISPE / FDA acceptance criteria (Mean ≥ 70%, %RSD ≤ 20%).

Rinse limit (mg/L) derived from MACO and total rinse volume, with analytical method LOQ suitability check. Full formula, variable definitions, and step-by-step tutorial.

Assesses whether visual inspection alone is adequate cleaning verification by comparing Surface Residue Limit (SRL) against Visual Detection Threshold (VDT), with adequate / marginal / inadequate verdicts.

USP <643> process-based TOC acceptance limit derived from MACO and % carbon, for rinse water or swab sampling. Governing limit is the more stringent of process-based and 500 ppb.

Acceptance Value (AV) per USP <905> Uniformity of Dosage Units. Two-stage acceptance: Stage 1 (n=10, AV≤15), Stage 2 (n=30, AV≤25) with individual-unit range check — formulas and worked steps.

Single-point immediate-release dissolution acceptance test per USP <711>. Sequential S1/S2/S3 stages with Q-based criteria and individual-unit checks — full acceptance rules explained.

Multi-point modified-release dissolution acceptance per USP <711> Table 3. User-defined time points with NLT / NMT / Range criteria and sequential L1/L2/L3 stages.

Stratified-sample blend uniformity per FDA guidance / ISPE PQLI: mean within range, %RSD ≤ max, and every location within individual limits across 8–30 locations.

Dissolution profile similarity per Moore & Flanner (1996), FDA 1997 and EMA 2010: f1 (difference) ≤ 15 AND f2 (similarity) ≥ 50, with the ≤1-point-above-85% and ≥3-time-point rules.

Assay workflow with single- or multi-point calibration, second-standard recovery, bracketing standards, LOQ verification, and sample %LC per USP <1225> / ICH Q2(R1).

Multi-lot linear regression with 95% one-sided confidence limits per ICH Q1E §4.1. Lower (potency) or upper (degradant) limits, extrapolation caps, and slope/intercept poolability analysis.

Analytical method validation statistics per ICH Q2(R1) / USP <1225>: accuracy (% recovery by level), precision (repeatability + intermediate with F-test), linearity, and regression-based LOD/LOQ.

Limit of Detection & Quantitation by three methods simultaneously: Signal-to-Noise (3:1 / 10:1), Calibration Curve (3.3σ/b, 10σ/b), and Blank Response (x̄+3σ / x̄+10σ).

Process capability indices per AIAG SPC / ISO 22514: Cp, Cpk (short-term via MR̄/d₂) and Pp, Ppk (long-term), σ-level, DPMO, histogram, and verdict against 1.00 / 1.33 / 1.67 thresholds.

Individuals & Moving Range control chart per AIAG SPC / Montgomery: σ̂ = MR̄/d₂ (d₂ = 1.128), Western Electric rules 1–5 for signal detection, estimated or specified limits.

Shewhart X̄ and R or S control charts from subgrouped data with AIAG SPC constants (n = 2..25) and Western Electric rules 1–5. Estimated or specified control limits.

Exponentially Weighted Moving Average chart per AIAG SPC / Montgomery §9.3 for detecting small sustained shifts (0.5σ–2σ). Time-varying and steady-state limits with tunable λ and L.

Normal tolerance intervals per ISO 16269-6 / ASTM E2996: two-sided or one-sided bounds with specified coverage and confidence via the Wald-Wolfowitz / Wallis k-factor, plus in-spec assessment.

Measurement system analysis via two-way crossed ANOVA per AIAG MSA 4th Ed. Decomposes variation into Equipment, Operator, Interaction, and Part; reports %GRR and ndc with verdicts.

Detect statistical outliers in analytical data using Grubbs (ISO 5725-2), Dixon Q (ASTM E178), and Generalized ESD (Rosner 1983), with consensus verdict and USP <1010> assignable-cause guidance.

Acceptance sampling plans by attributes per ANSI/ASQ Z1.4 / ISO 2859-1: code-letter lookup with arrow rules, OC curve, LTPD, AOQL, and Accept/Reject verdicts.